Perfusion system and method for monitoring tissue oxygenation and reducing limb ischemia - Patents.com

Abstract

A perfusion system and method is provided in which an extracorporeal pump having a controller and a catheter / tubing set employed alone or in conjunction with an interventional or circulatory assist device withdraws blood from a patient's vasculature and reintroduces it at a controlled local pressure or flow rate to another location within the patient's vasculature without interfering with the operation of the interventional or circulatory assist device or surgical intervention to increase peripheral blood flow and reduce limb ischemia.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This disclosure claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 362,363, filed April 1, 2022, which is incorporated by reference in its entirety.

[0002] The present invention relates generally to systems and methods for reducing ischemia by monitoring tissue oxygenation and providing enhanced perfusion in a patient's limbs. Specifically, the systems and methods of the present invention may be employed in patients suffering from shock or trauma, or in patients suffering from existing peripheral arterial disease, for the treatment of any medical condition inducing limb ischemia, including thrombotic or thromboembolic vascular embolism, or during medical procedures involving the use of devices that impede vascular blood flow (e.g., cardiac or vascular surgery, coronary or cardiac catheter placement, insertion of cardiac assist devices, and / or subsequent treatments to address peripheral arterial disease, and / or surgeries or interventions requiring a tourniquet), or for other causes of acute limb ischemia. [Background technology]

[0003] A reduction in blood flow to and / or pressure within a patient's extremities, e.g., legs and arms, can result from any of several causes, resulting in acute or chronic ischemia of the limb. During an interventional procedure, such as a percutaneous cardiac intervention, such as stent placement, heart valve repair, or coronary or cardiac catheter placement, a catheter can be placed within the patient's vasculature, which occludes flow within that vessel. Similarly, placement of a circulatory assist device within a vessel, such as a percutaneous ventricular assist device (pVAD), an intra-aortic balloon pump (IABP), or a cannula for an extracorporeal membrane oxygenation system (ECMO), can occlude downstream flow near the entry point of the circulatory assist device.

[0004] Reduced flow to the limbs can also result from cardiogenic shock, caused, for example, by myocardial infarction, myocarditis, pulmonary embolism, venous thrombosis, heart valve or myocardial tear, and many other disease conditions, many of which manifest as an inability of the patient's heart to pump sufficient oxygenated blood to the body's organs. Reduced circulation due to cardiogenic shock can lead to chronic ischemia of the patient's limbs, which in turn can require amputation. Reduced peripheral circulation can also result from existing peripheral arterial disease as a side effect of peripheral vascular intervention.

[0005] In addition, limb ischemia can also occur with the use of medical tourniquets, which are commonly used in conditions of vascular trauma or during surgery, such as knee surgery, to reduce bleeding into the surgical field. Tourniquets reduce both arterial and venous blood flow and can induce limb ischemia if used for extended periods of time. In these cases, the present invention allows for arterial and venous blood flow, respectively, using two bypass circuits for each, thereby preserving limb perfusion with the tourniquet in place.

[0006] One approach to increase blood flow to limbs in patients suffering from poor peripheral circulation due to obstruction caused by placement of an interventional device (e.g., catheter shaft or cannula) or circulatory assist device (pVAD or IABP) in the iliac, femoral, or axillary artery is to create an extracorporeal shunt using tubing from a location upstream of the obstruction to a cannula inserted into a remote location downstream of the obstruction in the patient's arterial system. U.S. Patent No. 9,782,279 to Kassab is an example of such a passive perfusion system. However, such proposed solutions have been observed to be ineffective in reducing limb ischemia, require ad-hoc settings, and are associated with a very high incidence of adverse outcomes, including prolonged hospital stays, limb amputations, and increased mortality.

[0007] Furthermore, quite apart from limb ischemia, medical complications can arise due to the sudden and catastrophic accumulation of blood within the pericardium, which impedes cardiac function and thereby reduces systemic circulation. One approach to reducing blood accumulation within the pericardium is to repeatedly manually aspirate blood from the pericardium. This is done until the patient can be transferred to the operating room, which can take 1 to 4 hours.

[0008] In light of the foregoing, it would be desirable to provide a system and method that overcomes the shortcomings of the aforementioned known solutions for monitoring tissue oxygenation and / or increasing blood pressure and flow to a patient's limb undergoing an interventional procedure or on a circulatory support device where an interventional device, circulatory support device, tourniquet, or other natural cause (i.e., thrombus formation) creates an occlusion in any artery or vein (i.e., iliac, femoral, axillary, brachial artery or vein). In particular, it would be desirable to provide an apparatus and method for enhancing blood flow and maintaining blood pressure in the peripheral vasculature sufficiently to secure the limb.

[0009] Additionally, it would be desirable to provide devices and methods for enhancing peripheral blood flow, particularly which reduces blood stagnation adjacent to a catheter or cannula insertion site, thereby reducing the risk of thrombus formation.

[0010] Still further, it would be desirable to provide apparatus and methods for increasing peripheral blood flow in patients undergoing vascular interventions or other surgical procedures, including the use of a tourniquet, and in patients recovering from peripheral vascular interventions, that are designed to reduce the risk of blood leaks at the device insertion site. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] U.S. Pat. No. 9,782,279 Summary of the Invention [Means for solving the problem]

[0012] The present invention is directed to systems and methods for monitoring tissue oxygenation, vascular or local pressure, and / or increasing peripheral blood flow and vascular pressure to reduce limb ischemia in patients suffering from arterial or venous occlusion due to disease conditions or due to cardiac or vascular interventions where an interventional device or tourniquet causes at least partial occlusion of downstream blood flow. In accordance with the principles of the present invention, the device of the present invention comprises an extracorporeal pump and a cannula / tubing set that may be used alone or in conjunction with any procedure or device that occludes blood flow, withdraws oxygenated blood from the patient's vasculature or anatomical compartment (i.e., the pericardium), and reintroduces that blood at an independently controlled vasculature pressure or flow rate to another location within the patient's vasculature. In this manner, blood flow or pressure may be independently controlled within the patient's limb without interfering with the placement or operation of an interventional or circulatory support device. In a preferred embodiment, flow may be adjusted to achieve a target vascular pressure to increase oxygenation of tissues within the limb that are experiencing or at risk of experiencing ischemia. Output from an infrared spectroscopy (NIRS) sensor or other oxygen sensing device applied to the affected limb may also be utilized as an input to the device of the present invention to adjust perfusion flow or pressure. Inlet suction pressure may also be used as a determinant of bypass flow.

[0013] In one preferred embodiment, the system of the present invention includes an inlet cannula configured to be placed in a patient's artery or vein, including a central lumen through which an interventional vascular device or circulatory assist device may be inserted. The inlet cannula may include a hemostatic valve and a side port through which blood passes from the inlet cannula to the inlet of the extracorporeal pump. The extracorporeal pump then propels the blood back into the patient's vasculature at a selected pressure or flow rate via a return lumen, which has an outlet downstream of the inlet cannula. In one embodiment, the outlet of the return lumen is embodied in a separate return cannula. In this embodiment, the return catheter may have a pressure sensor located near its outlet end to measure pressure within the vessel, and the pump output may be automatically adjusted to maintain a desired pressure within the vessel. In addition, an output from a NIRS sensor or other oxygen sensing device to monitor tissue oxygenation may be used to provide an input to a feedback loop that controls pump performance.

[0014] In alternative embodiments, the inlet cannula and the return lumen may be embodied in a single cannula. In one such implementation, the return lumen is a second lumen of the inlet cannula, opening to a skype in a lateral surface of the inlet cannula so that blood exiting the extracorporeal pump is returned to the vasculature downstream of the inlet cannula's inlet. An occlusion balloon may be placed near the distal end of the inlet cannula to partially or completely occlude antegrade blood flow through the artery so that blood is instead directed to the extracorporeal pump and blood returned from the pump does not flow in a retrograde direction. In this way, blood returned from the extracorporeal pump to the patient is delivered in an antegrade direction below the occlusion balloon to perfuse the patient's peripheral vasculature. The extracorporeal pump and / or cannula may include pressure and flow sensors for monitoring inlet and outlet pressures and blood flow rates, and the extracorporeal pump may include a controller for determining and maintaining a blood flow rate or pressure in the perfused vessel that is prescribed by a physician or determined automatically. The entry cannula may also include a balloon, separate from the occlusion balloon, to seal the cannulation site and prevent leakage.

[0015] According to another aspect of the invention, the occlusion balloon may have a concave profile on its proximal surface and be configured to direct flow exiting the skive of the return lumen in an antegrade direction. Alternatively, or in addition, the distal surface of the occlusion balloon may have a funnel shape when inflated to reduce the creation of stagnant blood areas. As yet a further alternative, the occlusion balloon itself may be perforated, such that blood directed into the balloon both expands the balloon into contact with the vessel wall, providing partial or complete occlusion, and then passes through the perforations, providing antegrade flow to the patient's limb.

[0016] In yet another embodiment, the perfusion system may include an inlet catheter inserted into the iliac, femoral, or axillary artery or vein, and a smaller diameter return catheter inserted through the lumen of the inlet catheter. An extracorporeal pump is configured to draw blood through an annulus formed between the interior of the inlet catheter and the exterior of the return catheter. Blood is delivered by the extracorporeal pump at a controlled pressure or flow rate through the return catheter back into the vasculature at a downstream location closer to the limb. In still further embodiments, the perfusion system may include multiple inlet cannulas for drawing blood from both the arterial and venous vasculature, and multiple return catheters for providing enhanced perfusion to multiple limbs. Additionally, multiple pumps or pump heads may be used that are independently controlled based on oxygenation, pressure, or flow input from a given area of ​​required perfusion.

[0017] Extracorporeal pumps suitable for use in the perfusion system of the present invention may comprise any suitable commercially available blood pump design, including vane pumps, centrifugal pumps, diaphragm pumps, piston pumps, and roller pumps. In one embodiment, the extracorporeal pump may be capable of generating pulsatile flow. In another embodiment, the extracorporeal pump may be capable of generating non-pulsatile flow.

[0018] Other features of the systems and methods of the present invention will become apparent with reference to the following description and drawings. [Brief description of the drawings]

[0019] [Figure 1] FIG. 1 is a schematic diagram of a perfusion system constructed in accordance with the principles of the present invention in which an extracorporeal pump is connected between an inlet catheter and a return catheter, through which an interventional or circulatory assist device may be placed.

[0020] [Figure 2A]2A and 2B are a schematic diagram of an alternative embodiment of a perfusion system of the present invention in which features of the inlet and return catheters of the embodiment of FIG. 1 are integrated into a dual lumen catheter, and a cross-sectional view of the dual lumen catheter, respectively. [Figure 2B] 2A and 2B are a schematic diagram of an alternative embodiment of a perfusion system of the present invention in which features of the inlet and return catheters of the embodiment of FIG. 1 are integrated into a dual lumen catheter, and a cross-sectional view of the dual lumen catheter, respectively.

[0021] [Figure 3A] 3A and 3B are further embodiments similar to the embodiment of FIG. 2, but further including an occlusion balloon for partially or completely occluding antegrade flow through the vessel, and a sealing balloon for preventing excess blood loss through the opening through which the perfusion cannula is inserted into the vessel. [Figure 3B] 3A and 3B are further embodiments similar to the embodiment of FIG. 2, but further including an occlusion balloon for partially or completely occluding antegrade flow through the vessel, and a sealing balloon for preventing excess blood loss through the opening through which the perfusion cannula is inserted into the vessel.

[0022] [Figure 4A] 4A and 4B are side views of an embodiment in which the inlet catheter includes a concave obliteration balloon to direct the reperfused blood, and another alternative embodiment in which a porous material is placed across the skive of the return lumen to more evenly distribute the reperfused blood within the vessel, respectively. [Figure 4B] 4A and 4B are side views of an embodiment in which the inlet catheter includes a concave obliteration balloon to direct the reperfused blood, and another alternative embodiment in which a porous material is placed across the skive of the return lumen to more evenly distribute the reperfused blood within the vessel, respectively.

[0023] [Figure 5A] 5A and 5B respectively show an embodiment in which the occlusion balloon and skive of FIG. 3 are replaced by a balloon having a distal portion that occludes antegrade flow and a proximal portion that is perforated through blood and returned to the vessel, and an alternative embodiment in which the distal and proximal faces of the balloon are inclined relative to the axis of the cannula to form a distal funnel and an enlarged proximal area for dispersing blood delivered by the extracorporeal pump. [Figure 5B] 5A and 5B respectively show an embodiment in which the occlusion balloon and skive of FIG. 3 are replaced by a balloon having a distal portion that occludes antegrade flow and a proximal portion that is perforated through blood and returned to the vessel, and an alternative embodiment in which the distal and proximal faces of the balloon are inclined relative to the axis of the cannula to form a distal funnel and an enlarged proximal area for dispersing blood delivered by the extracorporeal pump.

[0024] [Figure 6] FIG. 6 is another alternative embodiment of the perfusion cannula of FIG. 4 in which the occlusion balloon is inflated with blood delivered by the extracorporeal pump to partially or completely occlude antegrade flow, while the perforated proximal surface of the balloon disperses blood delivered by the extracorporeal pump to provide antegrade flow with controlled volume and pressure.

[0025] [Figure 7] FIG. 7 is a schematic diagram of a perfusion system of the present invention in which coaxial inlet and return catheters are coupled to an extracorporeal pump.

[0026] [Figure 8] FIG. 8 is an exemplary roller-type pump for providing pulsating flow that is suitable for use in the perfusion system of the present invention.

[0027] [Figure 9A] 9A, 9B, and 9C are schematic illustrations of the operation of a piston-style pump for generating pulsatile flow, suitable for use within the perfusion system of the present invention. [Figure 9B] 9A, 9B, and 9C are schematic illustrations of the operation of a piston-style pump for generating pulsatile flow, suitable for use within the perfusion system of the present invention. [Figure 9C] 9A, 9B, and 9C are schematic illustrations of the operation of a piston-style pump for generating pulsatile flow, suitable for use within the perfusion system of the present invention.

[0028] [Figure 10A] 10A and 10B are schematic block diagrams of an extracorporeal pump and software for use in an exemplary controller for controlling the operation of the extracorporeal pump, respectively, employed in the perfusion system of the present invention. [Figure 10B] 10A and 10B are schematic block diagrams of an extracorporeal pump and software for use in an exemplary controller for controlling the operation of the extracorporeal pump, respectively, employed in the perfusion system of the present invention.

[0029] [Figure 11] FIG. 11 is a screenshot of a display showing the results of near-infrared spectroscopy monitoring of limb oxygenation in an animal study in which the left limb of an animal is perfused by an embodiment of the present invention and the right limb is passively perfused.

[0030] [Figure 12A] 12A and 12B are graphs depicting tissue oxygenation and arterial blood gas values ​​for different animal studies demonstrating the difference between active and passive perfusion. [Figure 12B] 12A and 12B are graphs depicting tissue oxygenation and arterial blood gas values ​​for different animal studies demonstrating the difference between active and passive perfusion.

[0031] [Figure 13] FIG. 13 is another alternative embodiment of the perfusion system of FIG. 1 in which an extracorporeal pump is fed by two inlet cannulas and returns blood through one return cannula. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] Detailed Description of the Invention The present invention is directed to a perfusion system for monitoring tissue oxygenation and / or enhancing perfusion in a patient's limb that suffers from reduced blood flow to the limb due to any of several causes. Causes of such reduced blood flow may include placement of a percutaneous interventional or circulatory assist device in an artery or vein resulting in partial or complete occlusion of downstream blood flow in that vessel, or as a result of any procedure that requires interruption of blood flow, as a sequela of cardiogenic shock or peripheral arterial disease, or using a tourniquet or other method to stop blood flow to an area. In accordance with the principles of the present invention, the perfusion system draws arterial blood from a location upstream of the occluded or reduced flow area and delivers the blood back into the vessel, or into an adjacent or contralateral vessel, with controlled vasculature pressure or flow volume, thereby reducing the risk of limb ischemia. Additionally, flow to the limb through the pump may be regulated by physiological feedback, such as tissue oxygen levels.

[0033] Acute and / or chronic limb ischemia occurring in patients during vascular interventions is hypothesized to result from partial or complete obstruction of downstream arterial or venous flow created by blood clots, traumatic injury, tourniquets, or the presence of interventional device catheters or circulatory support devices. Other potential causes may include impaired cardiac output, arteriosclerosis, and / or a systemic increase in vascular hydraulic resistance in the limb, all of which may contribute to less flow in the limb at lower local pressures. Reduced peripheral flow and / or blood pressure may in turn contribute to increased thrombus formation, worsening limb ischemia, and increased risk of myocardial infarction, pulmonary embolism, and stroke. Thus, to address these challenges, the systems and methods of the present invention are designed to direct a portion of the blood flowing toward the limb to an extracorporeal blood pump that returns the flow to the same or another vessel at a controlled pressure or flow rate sufficient to reduce ischemia.

[0034] Other patients suffer complications of interventional procedures such as coronary artery perforation, cardiac rupture, right heart free wall puncture due to biopsy, or aortic or other valve rupture during valve replacement, which may develop rapid and catastrophic blood accumulation within the pericardium, thereby interfering with the function of the native heart. As excess blood is removed from the pericardium, the patient may require a blood transfusion to replace the aspirated blood. As excess blood is removed from the pericardium, the patient may require a blood transfusion to replace the aspirated blood. The systems and methods of the present invention are further designed to direct a portion of the accumulated blood to an extracorporeal blood pump, which returns the blood to the systemic circulation.

[0035] As mentioned in the background, some surgeons and interventional medicine clinicians have sought to increase flow to a patient's limbs by using tubing sets to passively transfer blood from higher pressure / flow areas, e.g., arteries proximate to the heart, into remote arterial locations, e.g., the femoral artery. Due to several factors, such attempts have not proven satisfactory due to the slow flow rates and low pressures inherent in such passive systems, as well as the hydraulic resistance encountered within the tubing sets. Applicants hypothesize that the presence of low vasculature pressures within the limb, even in the presence of substantial blood flow, may encourage inadequate oxygen absorption within the capillaries. It is Applicants' insight that by providing an extracorporeal blood pump, the blood flow rate and vasculature pressures delivered to a patient's limb may be better controlled to perfuse the limb and reduce the risk of ischemia. Additionally, the provision of one or more separate extracorporeal pumps allows the perfusion of the limb to be controlled independently from the operation of any vascular or circulatory assist devices that may create occlusions. The systems and methods of the present invention further enable a clinician to monitor perfusion within a patient's limb, adjust flow, and achieve targeted pressure within the perfused vessels in real time. When describing various embodiments, it should be understood that the terms "vascular pressure," "blood vessel pressure," "local pressure," "blood pressure," or some combination of these terms, refer to fluid pressure within a patient's blood vessels and / or capillaries.

[0036] 1, an exemplary perfusion system 10 arranged in accordance with the principles of the present invention is described. System 10 includes an inlet cannula 12, a return cannula 14, and an extracorporeal pump 16, which are joined by tubing 18. Inlet cannula 12 includes a proximal end 20 configured for placement within a femoral, iliac, or axillary artery or vein, and having an outlet port 22, through which an interventional or circulatory assist device may be inserted to perform an interventional procedure or assist cardiac function, and a hemostatic port 24. A distal end 28 of inlet cannula 12 is configured for placement in an antegrade orientation within the vessel to assist in positioning the interventional or circulatory assist device. Inlet cannula 12 has a sufficiently large diameter, e.g., 16-22 French, formed by an outer surface of the device through which annulus 30 is inserted and an inner surface of inlet cannula 12, such that blood flow will pass to outlet port 22 and to an inlet 32 ​​of pump 16.

[0037] In an alternative or additional option, the inlet cannula may be a pigtail catheter that is inserted into the pericardium in the event of blood accumulation within the pericardium. The accumulated blood is then drained from the pericardium and autotransfused through the return lumen into the vascular sheath. Such an embodiment would allow two life-saving therapies: 1) draining the pericardium so that blood does not accumulate and interfere with the function of the heart, and 2) autotransfusing the patient so that they do not require surplus blood products.

[0038] In one embodiment, the return cannula 14 may be configured to be placed in the patient's iliac, femoral, or axillary artery or vein with the outlet end 34 facing in a retrograde direction. In this orientation, blood delivered from the outlet 36 of the pump 16 through the lumen 38 of the return cannula 14 is directed toward the inlet cannula 12, causing flushing of any stagnant areas created where the inlet cannula 12 enters the vessel. The return cannula 14 may also include a valve 40 at its proximal end. At least a portion of the blood exiting the outlet end 34 of the return cannula 14 thus flows in a retrograde direction before flowing in an antegrade direction to the patient's limb. The return cannula 14 may also have an infusion port to allow the pump circuit to be used simultaneously for blood transfusion and / or one or more delivery ports for delivery of reperfusion protectants or therapeutic agents to reduce or eliminate reperfusion injury. Such reperfusion protection or therapeutic agents may include, but are not limited to, anticoagulants and thrombolytic agents.

[0039] In alternative embodiments, the return cannula may be configured to be placed at a more distal location in the peripheral circulation, away from the insertion site of the obturation sheath. For example, the return cannula may be placed in a vein or artery near the ankle when treating ischemia in the leg, or near the wrist when treating ischemia in the arm, even though the ankle or wrist may not be in the vicinity of the occlusion.

[0040] The extracorporeal pump 16 with display panel 17 may be a conventional commercially available blood pump capable of either continuous or pulsatile flow using any number of known pumping technologies, such as vane, diaphragm, gear, roller, centrifugal, axial, balloon-mounted, or piston pumps. In a preferred embodiment, the extracorporeal pump 16 is driven by an electric motor and includes a controller that allows vascular pressure or flow to be adjusted. The display panel 17 may be a touch screen device that allows the operation of the pump to be adjusted and displays the output of sensors located on the cannula. According to one aspect of the invention, the extracorporeal pump 16 may include or communicate with pressure sensors at the distal end 28 of the inlet cannula 12 and the outlet end 34 of the return cannula 14 to sense blood pressure, measure flow through the pump, and sense the presence of an occlusion. In such embodiments in which the pump controller communicates with a pressure sensor located in a vein or artery of the limb, it may be desirable to have the pressure sensor measure the local blood pressure through a lumen that is separate from any inlet or return lumen, such as the lumen described in FIGS. 2 and 3. The use of a separate lumen may allow the local pressure to be communicated or measured independently from the flowing blood. Those skilled in the art will appreciate that pressure sensors may also be located at the inlet port 32 and the outlet port 36. However, in such embodiments with pressure sensors at the inlet and outlet ports, it may be desirable to account for pressure drops caused by friction within the pump circuit. Such pressure drops may be accounted for by using a target pressure higher than the ideal target vascular pressure, reducing friction within the pump circuit, or a combination of the two. For example, it may be desirable to coat the inner surface of the cannula with a layer of polytetrafluoroethylene, such as Teflon®, to reduce friction within the pump circuit.

[0041] Further, in accordance with the present invention, the controller may include a processor programmed to sense vascular resistance at the outlet port 36. The controller may further be programmed to automatically adjust the outlet pressure and flow rate to maximize limb perfusion while avoiding the use of excess pressure that may cause extravasation and edema. In addition, the extracorporeal pump 16 may be configured to generate a pulsatile flow at the outlet 34 of the return cannula 14 that mimics the pressure rise and fall of a normal cardiac cycle, thus reducing the risk of thrombus formation. As a further option, the pump may be synchronized with an ECG output or pressure wave sensor to eject blood during diastole, thereby reducing afterload on the heart. Still further, the pump may be configured to oxygenate blood flowing through the pump when increasing vascular pressure or flow rate is insufficient. Those skilled in the art will recognize the possibility of joining a separate extracorporeal membrane oxygenation system (ECMO) to the pump circuit. In an alternative option, one inlet cannula may supply arterial blood to the pump, while venous and / or transfused blood may be pumped through the ECMO before being pumped into the pump. The pump then supplies a combination of this arterial blood and oxygenated venous and / or transfused blood through the return lumen.

[0042] According to another aspect of the invention, an extracorporeal pump may be configured to maintain a perfusion pressure rather than a selected output flow. For example, an extracorporeal pump may deliver blood such that the average perfusion pressure in a limb, e.g., a leg or arm, is maintained by continuously varying the flow rate. In addition, the supply of blood delivered to the pump may be from other parts of the body, e.g., an arm or other leg, rather than just upstream of the vessel into which the blood is being reperfused. Furthermore, the pump controller may be in communication with sensors that measure oxygenation of the blood and / or tissue in the limb being reperfused. Such sensors may use various measurement standards, such as, for example, blood oxygen saturation (SpO2), arterial blood gases (PaO2), near infrared spectroscopy (NIRS) levels to measure absolute tissue saturation (StO2), pH levels, or lactate levels. For example, the return cannula 14 may include an integrated NIRS sensor 35 proximate its distal end to measure tissue oxygenation levels of tissue surrounding the cannula at the reperfusion site. One example of an integrated NIRS sensor suitable for such use is described in an article entitled "Integrated near-infrared spectral sensing" by KD Hakkel et al. (Nature Communications, 13:103 (2022), available at https: / / doi.org / 10.1038 / s41467-021-27662-1). In this case, the controller of the extracorporeal pump may provide a readout on the display 17 of the flow rate, the local blood pressure in the perfused vessel, and the level of tissue oxygenation. The controller may also be programmed, for example, via the display panel 17, to allow the operator to select a combination of cycle length and outflow pressure that provides the highest flow rate at a target vessel pressure that achieves or maintains a target tissue oxygenation level.

[0043] Preferably, the controller of the extracorporeal pump has multiple operating modes. In each operating mode, the feedback loop that controls the pump is based on a different measured variable. In flow mode, the operator will manually set the flow rate at which the pump will perfuse the limb. In vascular or local pressure control mode, the system will perfuse the limb at a specific vascular pressure, the target pressure will be determined either manually or automatically. Similarly, in tissue oxygen control mode, the system will perfuse the limb to achieve a specific tissue oxygen level, the target oxygen level will be determined either manually or automatically. In any of these modes, the measured variables may be either manually entered or automatically determined by an artificial intelligence component. The controller software may also include an artificial intelligence component that prompts the controller to reassess the selected combination at various intervals of time and optimize the settings that work best for a particular patient. Alternatively, the pump circuit may serve as a passive bypass circuit until the controller senses, via sensor 35, a drop in tissue oxygenation levels that may result in limb ischemia. Once the controller senses a drop in tissue oxygenation levels below a predetermined value, the controller may automatically activate the pump.

[0044] According to another aspect of the invention, the pump may have two or more return cannulas, with each return cannula supplying blood to a different limb, each return cannula supplying blood to a different area or vein / artery of the same limb, or each return cannula supplying blood to different areas of multiple limbs, such as supplying blood to both the upper and lower portions of the leg while simultaneously supplying blood to the arm adjacent the shoulder and adjacent the wrist. In such embodiments, it may be desirable to maintain either a constant flow rate or a constant vascular pressure for some or all limbs being reperfused. Alternatively, the use of pressure control or flow control valves may be desired to vary the flow rate or pressure in one limb without changing the flow rate or pressure in another limb. The inlet cannula may alternatively be coupled to multiple pumps or a single pump with multiple stages, such that each pump or stage is employed to reperfuse a different limb. In such embodiments, each limb may maintain its own individual flow rate or vascular pressure. As another alternative, there may be multiple inlet cannulas, each supplying blood to the same or a different pump or motor. In such an embodiment, it may be desirable to have each inlet cannula inserted into a different vein or artery or transfusion blood supply. The blood reperfusion system may use any combination of multiple return and inlet cannulas and single or multiple pumps or motors. These inlet cannulas may then supply blood to either the same pump, two different pumps, or one or both inlet cannulas may supply blood to more than one pump. When both inlet cannulas are supplying blood to the same pump, the pump may have one or more return cannulas. When an inlet cannula is supplying blood to multiple pumps, each pump may have one or more return cannulas. When more than one return cannula is present, each return cannula may supply blood to a different limb, a different area of ​​the same limb, a different vein and / or artery of the same limb, or some combination of the foregoing.

[0045] For example, referring to FIG. 13, a pump 376 may have two inlet cannulas and one return cannula. The first inlet cannula may be an arterial inlet cannula 318 inserted into the limb's artery 332, while the second inlet cannula of the pump 376 is an oxygenation inlet cannula 316 that carries oxygenated blood from the ECMO 320. The ECMO 320 may be supplied by a venous inlet cannula 314 and a transfusion cannula 312, which supplies transfusion blood 310 to the ECMO. The blood supplied to the pump 376 by the arterial inlet cannula 318 and the oxygenation inlet cannula 316 is then mixed before being returned to the vein or artery 334 through the return cannula 322. One skilled in the art will appreciate that there are any number of other possible combinations. For example, the pump may have three inlets. That is, one inlet for transfused blood, one inlet for venous blood, and one inlet for arterial blood. In such an embodiment, ECMO may be omitted, or it may oxygenate only one of the transfused blood, venous blood, or arterial blood. The pump may also have more than one return cannula, with each return cannula returning blood to a different area of ​​the limb or to a different limb. In such an embodiment, the pump may or may not mix the inlet blood before feeding it to the return cannula. As a further option, the reperfusion system may have more than one pump or motor. For example, there may be a single pump or motor per inlet and / or per return. In another example, there may be one pump or motor for the venous inlet cannula and one pump or motor for all the arterial inlet cannulas.

[0046] According to another aspect of the invention, the device may be used to provide flow to one or more vascular compartments. For example, using a single motor and a single console, or separate motors and consoles, two rotors can be used to bypass two arteries, or an artery and a vein, or two veins. This is particularly useful when complete blockage to blood flow to and from the limb occurs, or is required, such as in the case of a tourniquet. In this case, the device would provide antegrade arterial flow to the limb and retrograde venous flow from the leg. This would allow optimal limb perfusion. In another embodiment, a multi-rotor device can provide arterial bypass to both legs, or to the leg and arm simultaneously.

[0047] 2A and 2B, an alternative embodiment of a perfusion system constructed in accordance with the principles of the present invention is described. Perfusion system 50 is designed to provide similar functionality to system 10 of FIG. 1, but employs a dual lumen cannula 52 instead of separate inlet and return cannulas. Cannula 52 includes a distal end 54 having an inlet 55, a valved inlet port 58, an outlet port 60, and a proximal end 56 having a hemostatic valve 62 through which an interventional or circulatory assist device 64 may be inserted. As depicted in FIG. 2B, cannula 52 has an inlet lumen 66 and an outlet lumen 68 that opens to a skive 70 at a location proximal to distal end 54. A NIRS sensor 69 may be located downstream of skive 70 to sense tissue oxygenation within the reperfusion region. Inlet lumen 66 is large enough so that an annulus 72 is formed around shaft 74 of device 64 such that extracorporeal pump 76 may draw blood from the vessel through inlet 55, annulus 72, and inlet port 58 at distal end 54. Extracorporeal pump 76 is coupled to inlet port 58 and outlet port 60 of cannula 52 via tubing 78 such that blood exiting pump 76 passes through outlet port 60, lumen 68, and skive 70. Pump 76 may include a built-in display panel 77 that serves as both an input device and a display screen.

[0048] The extracorporeal pump 76 may be configured as described with respect to the embodiment of FIG. 1 and preferably includes pressure and flow sensors at the distal ends of the inlet and return cannulas for monitoring flow characteristics such as local blood pressure and flow rate. In addition, the pump 76 may be configured to provide pulsatile flow to the skive 70 to perfuse the limb at a controlled pressure or flow rate. Although the skive 70 faces the vessel wall, it is expected that the throughflow lumen 68 will be sufficient to locally move the cannula 52 away from the vessel wall and allow blood to flow freely in the antegrade direction.

[0049] 3A and 3B, a further alternative embodiment of the perfusion system of the present invention is described. System 80 includes a multi-lumen cannula 82 coupled to an extracorporeal pump 84 via tubing 86. An extracorporeal pump 84 suitable for use with cannula 82 may have any of the features for the embodiments described with respect to the perfusion system of Figures 1 and 2. Cannula 82 is similar in design to cannula 52 of the embodiment of Figures 2A and 2B, except that it further includes an embolization balloon and an optional sealing balloon.

[0050] More specifically, cannula 82 includes a distal end 88 having an inlet 89, a proximal end 90 having valved inlet and outlet ports 92 and 94, balloon inflation ports 96 and 98, and a hemostatic valve 100 through which an interventional or circulatory assist device 102 may be inserted. As shown in FIG. 3B, cannula 82 has inlet lumen 104, balloon inflation lumens 106 and 108, and an outlet lumen 110 that opens to a skive 112 at a location proximal to distal end 88. Inlet lumen 104 is sufficiently large so that an annulus 114 is formed around shaft 116 of device 102 such that extracorporeal pump 84 may draw blood from the vessel through inlet 89, annulus 114, and inlet port 110 at distal end 88. Extracorporeal pump 84 is coupled to inlet port 92 and outlet port 94 of cannula 82 via tubing 86 such that blood exiting pump 84 passes through outlet port 94 , lumen 110 , and skive 112 .

[0051] 3A and 3B, the cannula 82 further includes an embolization balloon 118 disposed between the distal end 88 and the skive 112 to partially or completely occlude antegrade flow through the vessel, and an optional elongated sealing balloon 120 disposed proximal to the skive 112 to reduce blood leakage around the cannula 82 where it enters the vessel. The embolization balloon 118 is in fluid communication with the inflation port 96 via the inflation lumen 106 and with an opening 122 that opens to the interior of the embolization balloon 118. Similarly, the sealing balloon 120 is in fluid communication with the inflation port 98 via the inflation lumen 108 and with an opening 124 that opens to the interior of the sealing balloon 120. The embolization balloon 118 is preferably made of a semi-compliant material such as nylon, or a compliant material such as polyurethane, which allows the balloon to conform to the diameter of the vessel and partially or completely embolize antegrade flow. The sealing balloon 120 is preferably made of a more rigid material such as polyethylene terephthalate, which retains its shape during expansion and provides a close proximity to the entry wound through which the cannula 82 is inserted into the vessel. Notably, the sealing balloon 120, if provided, may be inflated via the inflation port 98 if the insertion site begins to bleed during operation of the pump 84, thus stopping the bleeding and directing blood exiting the skive 112 toward the patient's extremities.

[0052] 4A and 4B, an alternative structure for more evenly distributing blood exiting the skive 70 of the cannula 52 of FIG. 2 or the skive 112 of the cannula 82 of FIG. 3 is now described. In FIG. 4A, a portion of the cannula 82 of FIG. 3 is depicted having a plurality of skives 112′ and an embolization balloon 118′ disposed distally of the skives 112′. When inflated, the embolization balloon 118′ assumes a concave shape 125 such that blood exiting the skive 112′ impinges on a proximal surface of the balloon and is redirected in an antegrade direction. The embolization balloon 118′ may be molded to assume the concave shape 125 during manufacture. In this manner, blood reperfused into the vessel from the extracorporeal pump may be more evenly redistributed and directed in an antegrade direction within the vessel without impinging directly on the vessel wall.

[0053] 4B shows an alternative structure that may be used to distribute the returned flow through the skive 70 of the cannula 52 or the skive 112 of the cannula 82. The diffuser 130 comprises a thin-walled layer of shrink tubing 132 that includes multiple holes 134 and is affixed to the cannula over the skive 70 of the cannula 52 or the skive 112 of the cannula 82 to more evenly distribute the blood returned from the extracorporeal pump. In particular, the diffuser 130 may be bonded to the cannula using heat welding or a suitable biocompatible adhesive glue along line 136. The diffuser 130 reduces the risk that blood returned to the vessel through the skive will propel against the vessel wall at high velocity. In addition, the diffuser 130 may be easily flushed with saline prior to use without making the cannula bulky or interfering with insertion. In such an embodiment of FIGS. 3A and 3B, it may be desirable to place a local blood pressure sensor in the vessel downstream of the diffuser 130.

[0054] 5A and 5B depict additional modifications that may be made to the cannula 82 of the embodiment of FIGS. 3A and 3B. FIGS. 5A and 5B depict the distal end of a perfusion cannula (e.g., cannula 82) and omit any interventional or circulatory assist devices that may extend through the inlet lumen and distal end of the cannula. In the embodiment of FIG. 5A, the occlusion balloon 118 and skive 112 are combined into a bilayer balloon 140. The balloon 140 may be formed from a semi-compliant material such as nylon or a compliant material such as polyurethane, and includes an upper section 142 separated from a lower section 144 by a fluid-impermeable membrane 145. The sealed upper section 142 is configured to expand into contact with the vessel wall when filled with saline through the opening 122. The lower section 144 includes a lower surface 146 in fluid communication with the skive 112 and having a number of perforations 146.

[0055] In the arrangement of FIG. 5A, the upper section 142 of the balloon 140 serves to partially or completely occlude the vessel while the lower section 144 delivers blood to the distal vessel. Optionally, a separate balloon may be used in place of the bilayer balloon 140, but the bilayer construction of the balloon 140, more preferably a disk-shaped one, may be desirable to shorten the balloon so that it can be easily inserted into highly arteriosclerotic vessels. In addition, the multiple perforations 148 will ensure that blood is reperfused into the vessel away from the vessel wall. FIG. 5B depicts an alternative embodiment of a bilayer balloon with seals and perforated sections similar to the design of FIG. 5A. The bilayer balloon 150 differs from the balloon 140 primarily in that the upper surface of the balloon 150 forms a funnel shape 152, while the perforated lower surface 154 of the balloon is also inclined relative to the vessel wall, further distributing the reperfused blood into the vessel. In such an embodiment of FIGS. 5A and 5B, it may be desirable to place a vascular pressure sensor within the vessel downstream of the perforated lower surface 154.

[0056] Referring now to FIG. 6, a further alternative embodiment of the perfusion system of the present invention is described. In FIG. 6, elements of the system common to the embodiments of FIG. 2A and FIG. 3A are omitted for clarity. Cannula 160 is a dual lumen cannula, as described above with respect to FIG. 2A. Balloon 162 is affixed to the cannula through which blood is delivered into the vessel by an extracorporeal pump (e.g., pump 76 of FIG. 2A) such that the interior of balloon 162 is in communication with skive 164. Balloon 162 includes multiple perforations 166 in its underside surface. In this manner, balloon 162 expands and at least partially occludes the vessel when blood from the extracorporeal pump is delivered into the interior of balloon 162. Blood then exits balloon 162 through multiple perforations 166 and flows in an antegrade manner to the patient's extremity. In such an embodiment of FIG. 6, it may be desirable to place a vascular pressure sensor in the vessel downstream of balloon 162.

[0057] FIG. 7 depicts a further alternative embodiment of a perfusion system constructed in accordance with the principles of the present invention. System 170 differs from the previously described embodiments in that an inlet catheter may be employed to perform an interventional procedure, e.g., to treat peripheral arterial disease, and then used as part of a perfusion system to reduce the risk of limb ischemia. As depicted in FIG. 7, system 170 includes an inlet cannula 172 and a return catheter 174 coupled by tubing 178 to an extracorporeal pump 176. Extracorporeal pump 176 may be any of the pumps described throughout this specification.

[0058] Inlet cannula 172 has a distal end 180 having an inlet 182, an outlet port 186, a hemostasis port 188, and a proximal end 184 that includes an inlet lumen 190 extending between the distal end 180 and the proximal end 184 and is in fluid communication with the outlet port 186. Inlet cannula 172 is configured to be placed in an extremity, such as an arm or leg, in an antegrade manner to perform an interventional procedure. Once the treatment is completed, inlet cannula 172 may be left in place and employed as part of a perfusion system, as described below.

[0059] Return cannula 174 has a proximal end 192 including an inlet port 194, an outlet 196, and a lumen 198 extending therebetween. Return cannula 174 is preferably longer than inlet cannula 172 and has a diameter selected such that when inserted through inlet cannula 172, an annulus 200 is created in inlet lumen 190, allowing blood to be drawn through inlet 182, annulus 200, and outlet port 186 into the extracorporeal pump 176. Return catheter 174 is inserted through hemostasis port 188. The inlet and outlet cannulas may then be coupled to the extracorporeal pump 176 by tubing 178. In operation, pump 176 draws blood into the pump through inlet 182, annulus 200, and outlet port 186, and then expels the blood in the antegrade direction through inlet port 194, lumen 198, and outlet 196 of return cannula 174 into the vasculature at a controlled pressure or flow rate as determined by pump 176 based on user input or by a pump controller. Alternatively, return cannula 174 may be placed in the patient's contralateral arm or leg, as may be required to reduce the risk of limb ischemia.

[0060] In yet further embodiments, an inlet cannula may be inserted into more than one artery or vein, and blood delivered by the extracorporeal pump may be reperfused into more than one limb. For example, the extracorporeal pump may include two or more inlets, such that one inlet may be connected to a cannula located in an artery, and a second inlet may be coupled to a cannula placed in a vein of the limb. Blood delivered by the extracorporeal pump may be reperfused into an artery downstream of the occlusion, while venous blood may be drawn from the limb, thereby creating an additional gradient to enhance perfusion of the limb. Alternatively, the extracorporeal system of the present invention may be configured to have a single inlet but multiple outlets, such that oxygenated blood directed to the pump may be reperfused into multiple limbs. In another alternative embodiment, the return cannula may deliver blood to the afferent lymphatic vessels of the lymphatic system to reduce or prevent venous thrombus formation, peripheral edema, or lymphedema.

[0061] Referring now to FIG. 8, an exemplary mechanism 210 for a roller-type pump suitable for use as an extracorporeal pump in a perfusion system is shown. As would be understood by one skilled in the art of pump design, the mechanism 210 includes a rotor 212 carrying three or more rollers 214. The rollers 214 contact plastic tubing 216, which tubing is connected to an inlet port 218 and an outlet port 220 of the pump. The rotor 212 is mounted on an axle 222 that is coupled, either directly or through a suitable gear train, to an electric motor (not shown) such that rotation of the rotor causes the rollers 214 to ride along the plastic tubing 216 and propel blood within the tubing from the inlet port 218 to the outlet port 220. U.S. Patent No. 3,963,023 to Hankinson (incorporated herein by reference) provides additional details regarding roller pumps of the type depicted in FIG. 8. A suitable alternative blood pump design capable of generating pulsatile flow is described in U.S. Patent No. 9,295,767 to Schmid, also incorporated herein by reference. U.S. Patent No. 4,468,177 to Strimling describes a diaphragm-type pump suitable for use as the extracorporeal pump of the perfusion system of the present invention, also incorporated herein by reference.

[0062] 9A, 9B, and 9C, a piston-type mechanism for use as an extracorporeal pump in the system of the present invention is described. Pump 230 includes a piston 232 arranged for reciprocating movement within a chamber 234 in communication with an inlet 236 and an outlet 238. As would be understood by one skilled in the art of pump design, piston 232 is coupled to an electric motor via a gear system (not shown), which cyclically advances and retracts a piston head within chamber 234. A one-way valve 240, e.g., a butterfly valve or flap valve, is located distal to inlet 236, and another one-way valve 242 is located proximal to outlet 238. A pressure sensor 244 monitors the pressure in a conduit distal to outlet 238. In FIG. 9A, pump 230 is shown in an equilibrium condition in which no blood is being drawn into or expelled from chamber 234. If the pressure sensor 244 detects high pressure in the conduit while the vascular pressure sensor detects low pressure, this may indicate that the tubing is blocked, clotted, or kinked. The controller may signal an alarm based on detection of a pressure differential exceeding a predetermined threshold.

[0063] 9B depicts the intake stroke of pump 230 during which inlet valve 240 opens to allow blood to be drawn into chamber 234 during retraction of piston 232. During this phase of operation, one-way valve 242 is closed and pressure sensor 244 detects a negative pressure. Once the piston reaches its minimum stroke, it reverses direction, closing one-way valve 240 and opening one-way valve 242, thus allowing blood to flow through outlet 238. During this phase of operation, pressure sensor 244 detects a positive pressure. Once piston 232 reaches its maximum stroke, it begins to reverse direction, thereby closing one-way valve 242 and opening one-way valve 240 again. Thus, depending on the speed at which the electric motor and gear train drive piston 232, a defined blood flow rate or pressure may be obtained at outlet 238. Child, U.S. Pat. No. 4,221,548, describes an alternative embodiment of a piston pump, which is suitable for use within the perfusion system of the present invention, and is incorporated herein by reference.

[0064] 10A and 10B are exemplary schematic diagrams of an extracorporeal pump and software for operating the system, respectively. More specifically, FIG. 10A is a schematic diagram depicting the functional blocks of an extracorporeal pump 250 for use in the perfusion system of the present invention, including a processor 252 coupled to a non-volatile memory 254, such as a flash memory, an electrically erasable programmable read-only memory, and / or a hard disk, and a volatile memory 256 via a data bus. The processor 252 is electrically coupled to an electric motor 258, a number of sensors 260, a user interface 262, and a valve controller 264. The motor 258 may include a separate dedicated controller that interprets commands from the processor 252 and operates the motor 258 in response thereto.

[0065] 10B, stored in non-volatile memory 254, which controls operation of motor 258 in response to signals generated by sensors 260 and input from user interface 262. Processor 252 is configured to monitor operation of motor 258 (and any associated motor controller) and sensors 260, and to store data reflecting the operation of the pump, including event logs and alarms, as described below.

[0066] Non-volatile memory 254 preferably includes flash memory, EEPROM, or solid state or hard disk and stores a unique device identifier for the pump, and firmware and configuration set point data related to programming to be executed by processor 252 and operation of the pump. Volatile memory 256 is coupled to processor 252 and supports its operation, storing data and event log information collected during operation of pump 250.

[0067] The motor 258 is of a type selected to drive the pumping mechanism of an extracorporeal pump such as those described above. The user interface 262 may include an input device, for example corresponding to the display panels 17 and 77 described above, or may include input keys and a display for displaying entered pump operating parameters, pump status, and sensed data. The sensors 260 may include pressure sensors at the inlet and outlet ports of the pump, pressure sensors in the artery or vein downstream of the inlet of the inlet cannula and downstream of the outlet of the return cannula, blood and / or tissue oxygenation sensors such as NIRS, pH and / or lactate level sensors, and flow sensors for determining the flow rate of blood through the pump. The sensors 260 may be monitored by the processor 252 to determine inlet and outlet blood pressure, tissue oxygenation, and the occurrence of occlusions in the blood circuit.

[0068] The processor 252 may be in communication with a valve controller 264, or alternatively, the valve controller 264 may be part of the functionality of the processor 252. The valve controller 264 controls the operation of any valves that may be used to control the flow of blood from an inlet port to an outlet port. The valve controller 264 may also coordinate the operation of one-way valves in the embodiment of FIGS. 9A-9C.

[0069] 10B, software 270 for operating the extracorporeal pump 250 of FIG. 10A will be described. It should be understood that the software 270 is implemented as programming that is initiated by the processor 252 and that controls, among other things, the operation of the extracorporeal pump's motor 258. The software 270 comprises several functional blocks, including a main block 272, a sensor block 274, an alarm detection block 276, an event logging block 278, a user interface block 280, a configuration setting block 282, and an AI module 284. In one embodiment, the software is configured to run on a Microsoft Windows® (registered trademark of Microsoft Corporation, Redmond, Wash.) or Unix® based operating system.

[0070] The main block 272 preferably consists of a main software routine that executes on the processor 252 and controls the overall operation of the other functional blocks. The main block 272 allows an operator to input operational data about the pump via the user interface 280 and the user interface 262, and to display operational and status data about the pump, including pump outlet pressure and / or flow rate, local blood pressure, tissue oxygenation levels, and alarm limit data. The main block 272 also controls the operation of the motor 258 and the monitoring of sensors via the sensor block 274.

[0071] The alarm detection block 276 may include routines for evaluating data received from the sensor 260 and determining the occurrence of an abnormal condition for the operator's attention. For example, the alarm detection block 276 may be configured to alert the operator to deviations in sensor data from pre-set values ​​or to identify potential occlusions or displacement of the catheter from the vascular lumen in affecting pump operation. The alarm detection block 276 may also be configured to detect increases in vascular resistance and / or pressure within the patient's limb, as well as potentially slow flow conditions that may lead to limb ischemia. Additionally, the alarm detection block 276 may be configured to detect decreases in limb tissue oxygenation. Such alarms may be communicated to the operator via a display on the user interface 262. This information may be stored in the non-volatile memory 254 by the event log block 278 to generate a record of pump operation data, including pump operation times and pressure / flow data.

[0072] The user interface block 280 handles the receipt of data entered by the operator and the display of information about pump operation status in an intuitive, easily understood format for operator review. The configuration block 282 is a routine that configures parameters stored in the non-volatile memory 254 that control the operation of the pump 250, including the required pump output pressure, local blood pressure, flow rate, tissue oxygenation, and any limits used to assess the occurrence of an alarm condition. The block 282 may also configure parameters stored in the non-volatile memory 254 that are associated with controlling the operation of the processor 252 and the motor 258.

[0073] The AI ​​module block 284 may include programming that enables the extracorporeal pump to automatically optimize the local blood pressure and tissue oxygenation levels for a particular patient and reduce the risk of limb ischemia. In particular, the AI ​​module 284 may include programming that initiates pump operation at a pressure and / or tissue oxygenation level initially set by a human operator. Then, based on monitored pressure data from the limb and / or monitored tissue oxygenation levels, the AI ​​module may step through a series of pump speeds and adjust the flow rate while also monitoring the pressure within the patient's limb. In one embodiment, the AI ​​module 282 may then continue further operation of the pump by selecting the pump speed that produces the highest monitored flow rate at the lowest pressure.

[0074] In an alternative embodiment, the AI ​​module 282 may be configured to activate an integrated or in-line ECMO system if it is determined that the increased flow rate or local blood pressure is not sufficient to maintain a target level of oxygenation in the tissue of the limb. In a further embodiment, the AI ​​module 282 may activate the ECMO, causing hyperbaric oxygenation of the blood to further increase tissue oxygenation. In yet another embodiment, the pump circuit may act as a passive bypass until the sensor 260 detects a tissue oxygenation level dropping below a target value. Once the tissue oxygenation level is detected dropping below a target value, the AI ​​module 282 may then activate the pump to increase the local blood pressure in the reperfusion area.

[0075] Preliminary Experimental Observations Initial testing of the proposed reperfusion pump system and method of the present invention has been conducted in a porcine model, and the results of that testing have demonstrated unexpected and beneficial results, as described below.

[0076] Vascular Pressure Controlled Pump vs Passive Bypass FIG. 11 is a screenshot of a display depicting vascular blood pressure and oxygen saturation in a pig's leg. In this experiment, the pump circuit of the present invention was used to generate a blood circuit from the carotid artery to the left leg (top graph), while a passive circuit was generated by tubing inserted into the other carotid artery at one end and into the right leg at the other end (bottom graph). In both legs, continuous NIRS measurements were taken to determine absolute tissue saturation (StO2) levels through various stages of the reperfusion process, and the digital readout to the right of the graphs shows the StO2 levels at the end of the experiment. The top line of each graph shows the baseline value of the non-occluded area of ​​the animal (81% for the right leg and 73% for the left leg). The bottom line of the top graph (shown as 77% StO2) corresponds to the NIRS measurement of the StO2 levels in the left leg (with the pump circuit of the present invention) after occlusion of that leg. The bottom line in the bottom graph (designated as 55% StO2) corresponds to NIRS measurements of StO2 levels in the right leg with passive bypass only.

[0077] At the start of the NIRS measurements, both legs were embolized without any form of reperfusion to reduce the StO2 level in each leg. Once the quasi-static level was reached, NIRS measurements were recorded for 5 minutes before reperfusion was initiated. At the 5 minute mark, as noted by the asterisk (*), both the passive bypass and the pump system of the present invention were activated. In the left leg (top graph), it can be seen that the vascular pressure controlled perfusion resulted in higher perfusion of the leg tissue, as indicated by the steep curve that ends at 77% StO2. The right leg (bottom graph) shows that the passive bypass has less reperfusion value, as indicated by the flat curve that ends at 55% StO2. The experiment demonstrates that the passive system does not oxygenate the tissue to the same extent as the pump circuit of the present invention, where vascular blood pressure is controlled.

[0078] Absolute tissue saturation (StO2) and blood oxygen pressure (PaO2) 12A and 12B show the results of a second experiment in which flow was occluded (the iliac artery was blocked) to induce ischemia in one leg of a pig, followed by passive bypass reperfusion and then vascular controlled pressure reperfusion using the pump system of the present invention. FIG. 12A depicts the StO2 levels during five sequential intervals, while FIG. 12B depicts the PaO2 levels during the same five intervals. Time point 1 represents the basal levels of StO2 and PaO2 measured before occlusion occurred. Time point 2 corresponds to 20 minutes of ischemia-inducing occlusion of the leg, as indicated by the extreme drop in both levels. Time point 3 corresponds to the provision of passive bypass for approximately 15 minutes, which ends at time point 4. Notably, during passive bypass, blood oxygenation levels rise substantially (to 246.9), but tissue oxygenation, as determined by NIRS measurements, shows virtually no increase, from 27% StO2 to only 28% StO2. At time point 4 in Figures 12A and 12B, passive bypass was terminated for approximately 90 seconds, returning the limb to an ischemic state. Then, at time points 4 to 5, the vascular pressure controlled system described herein was activated. After 1 minute, blood oxygenation levels returned to normal, from 128.8 PaO2 to 315.5 PaO2. Importantly, however, tissue oxygenation, as measured by the NIRS sensor, also rose significantly, from 15% StO2 to 41% StO2. The above preliminary results demonstrate that reperfusing an ischemic limb at controlled vascular pressure provides much more oxygen uptake than simply flowing physiological flow rates. Applicants hypothesize that vascular blood pressure induces higher oxygen exchange within the capillary beds of the limb than could be achieved by simply providing physiological flow rates to the reperfused vessels.

[0079] While various illustrative embodiments of the present invention are described above, it will be apparent to those skilled in the art that various changes and modifications can be made thereto without departing from the invention.

Claims

1. 1. A perfusion system for use with an obstruction of antegrade flow to a patient's limb due to thrombus formation, trauma, or a medical procedure / device, the perfusion system comprising: an inlet cannula configured to be placed in a patient's vasculature, the inlet cannula having a proximal end, a distal end, a lumen extending from the proximal end to the distal end, an inlet at the distal end, an outlet port, and a hemostasis port disposed on the proximal end, the inlet and the hemostasis port communicating with the lumen, the hemostasis port configured to allow an interventional or circulatory assist device to be inserted through the lumen and form an annulus in communication with the outlet port; a return lumen having a proximal end and a distal end, the distal end of the return lumen configured to be placed in the patient's vasculature downstream of the occlusion; an extracorporeal pump configured to be coupled to the outlet port of the inlet cannula and to a proximal end of the return lumen; Equipped with The extracorporeal pump is configured to draw blood through the inlet of the inlet cannula and deliver blood to the distal end of the return lumen at a selected local pressure without interfering with the operation of the intervention or circulatory assist device.

2. The perfusion system of claim 1 , wherein the return lumen is disposed within a return cannula.

3. The perfusion system of claim 1 , wherein the return lumen comprises a second lumen of the inlet cannula, a distal end of the return lumen defining a skive in a lateral surface of the inlet cannula.

4. 10. The perfusion system of claim 1, wherein the inlet catheter further comprises an occlusion balloon for at least partially occluding flow within the vessel antegrade to the inlet cannula inlet.

5. 5. The perfusion system of claim 4, wherein the inlet catheter further comprises a first inflation port at a proximal end of the inlet cannula and a first inflation lumen extending through the inlet cannula from the first inflation port to the embolization balloon.

6. The inlet cannula further comprises: a sealing balloon disposed proximal to the embolization balloon; a second inflation port at a proximal end of the inlet cannula; a second inflation lumen extending through the inlet cannula from the second inflation port to the sealing balloon; The perfusion system of claim 4 , comprising:

7. 10. The perfusion system of claim 1, wherein the extracorporeal pump further comprises an extracorporeal membrane oxygenation system.

8. 10. The perfusion system of claim 1, wherein the extracorporeal pump is in communication with sensors that measure at least one of tissue oxygenation, pH levels, and lactate levels in the embolized limb and is programmed to adjust vascular pressure or flow rate to achieve a target tissue oxygenation level.

9. 2. The perfusion system of claim 1, wherein the return lumen comprises a second lumen of the inlet cannula, the inlet catheter further comprises an occlusion balloon having multiple perforations, and a distal end of the return lumen communicates with an interior of the occlusion balloon.

10. 10. The perfusion system of claim 1, wherein the extracorporeal pump is programmed with an AI module configured to automatically determine a preferred flow rate to achieve a target local pressure that reduces the risk of limb ischemia.

11. 2. The perfusion system of claim 1, wherein the extracorporeal pump is in communication with a pressure sensor located within the patient's vasculature antegrade relative to the distal end of the return lumen and is programmed to monitor the pressure sensor to determine the occurrence of an embolus.

12. 1. A perfusion system comprising: at least one inlet cannula configured to be placed within a patient's vascular system, the at least one inlet cannula having a proximal end, a distal end, a lumen extending from the proximal end to the distal end, an inlet at the distal end, and an outlet port disposed on the proximal end, the inlet in communication with the lumen; at least one return lumen having a proximal end and a distal end, the distal end of the at least one return lumen configured to be placed within the patient's vasculature at one or more locations downstream of an inlet of the at least one inlet cannula; an extracorporeal pump configured to be coupled to an outlet port of the at least one inlet cannula and a proximal end of the at least one return lumen; Equipped with The extracorporeal pump is configured to draw blood through an inlet of the at least one inlet cannula and deliver blood through a distal end of the at least one return lumen at a selected local pressure.

13. 13. The perfusion system of claim 12, wherein the at least one return lumen is disposed within at least one return cannula, the at least one inlet cannula further comprising a hemostasis port disposed on the proximal end, the hemostasis port configured to allow an interventional or circulatory assist device to be inserted through the lumen and form an annulus in communication with the outlet port.

14. 14. The perfusion system of claim 13, wherein the at least one return cannula is configured to be inserted through a hemostasis port of the at least one inlet cannula and form an annulus in communication with an outlet port of the at least one inlet cannula.

15. 13. The perfusion system of claim 12, wherein the extracorporeal pump is selected from among a vane pump, a centrifugal pump, a roller pump, an axial pump, a diaphragm pump, and a piston pump, and the extracorporeal pump is configured to generate pulsatile flow at a distal end of the return lumen.

16. 13. The perfusion system of claim 12, wherein the return lumen further comprises at least one delivery port configured to deliver one or more reperfusion protection agents or donor blood for transfusion.

17. The perfusion system of claim 12 , wherein the extracorporeal pump comprises an electric motor and a controller that controls operation of the electric motor.

18. 18. The perfusion system of claim 17, wherein the controller is programmed to maintain a selected local pressure at the distal end of the at least one return lumen via adjusting flow rate, the selected local pressure being input via a user interface.

19. 20. The perfusion system of claim 17, wherein the controller is programmed with an AI module configured to automatically determine a preferred flow rate to achieve a target local pressure that reduces the risk of limb ischemia.

20. 18. The perfusion system of claim 17, wherein the extracorporeal pump is in communication with a pressure sensor located in the patient's vasculature downstream of a distal end of the at least one return lumen, and the controller is programmed to monitor the pressure sensor to determine the occurrence of an occlusion, and the controller is programmed to generate an alarm if a monitored pressure sensor falls outside a preselected limit value.

21. 13. The perfusion system of claim 12, wherein the extracorporeal pump comprises a first extracorporeal pump and a second extracorporeal pump, the at least one inlet cannula comprising a first inlet cannula having a first inlet configured to be placed in a patient's vein and a second inlet cannula having a second inlet configured to be placed in a patient's artery, the first extracorporeal pump configured to draw blood through the first inlet and return the blood via the outlet to a vein distal to the occlusion, and the second extracorporeal pump configured to draw blood through the second inlet and deliver the blood via the outlet to an artery distal to the occlusion.

22. 13. The perfusion system of claim 12, wherein the extracorporeal pump comprises a first motor and a second motor, the at least one inlet cannula comprising a first inlet cannula having a first inlet configured to be placed in a patient's vein and a second inlet cannula having a second inlet configured to be placed in a patient's artery, the motor configured to draw blood through the first inlet and return the blood via the outlet to a vein distal to a thrombus, and the second motor configured to draw blood through the second inlet and return the blood via the outlet to an artery distal to a thrombus.

23. 1. A perfusion system for returning accumulated blood in a cavity of a patient to the systemic circulation, the perfusion system comprising: an inlet cannula configured to be placed within a cavity of a patient, the inlet cannula having a proximal end, a distal end, a lumen extending from the proximal end to the distal end, an inlet at the distal end, and an outlet port disposed on the proximal end, the inlet in communication with the lumen; a return lumen having a proximal end and a distal end, the distal end of the return lumen configured to be placed within a vasculature of a patient; an extracorporeal pump configured to be coupled to the outlet port of the inlet cannula and to a proximal end of the return lumen; Equipped with The extracorporeal pump is configured to draw blood through the inlet of the inlet cannula and deliver blood to the distal end of the return lumen at a selected local pressure.

24. 24. The perfusion system of claim 23, wherein the inlet cannula further comprises a hemostasis port in communication with the lumen, the hemostasis port configured to allow an interventional or circulatory assist device to be inserted through the lumen and form an annulus in communication with the outlet port.

25. 24. The perfusion system of claim 23, wherein the patient cavity is the pericardium.

26. 24. The perfusion system of claim 23, wherein the distal end comprises a pigtail catheter.

27. 24. The perfusion system of claim 23, wherein the return lumen further comprises at least one delivery port configured to deliver one or more reperfusion protection agents or donor blood for transfusion.

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