CN115052651A

CN115052651A - Infusion catheter and method of use

Info

Publication number: CN115052651A
Application number: CN202080081474.7A
Authority: CN
Inventors: R·D·舒尔茨; J·M·奥尔沙夫斯基; B·C·沃罕; C·泰根; S·泰根; M·E·萨拉米; N·S·车拉帕; A·R·R·耶卢鲁; A·K·库赖施; M·E·R·琼斯; A·J·肖; M·W·L·斯普林克尔; A·S·李; E·T·科雷特斯基; S·罗伊塞尔; R·沙菲尔
Original assignee: Penumbra Inc
Current assignee: Penumbra Inc
Priority date: 2019-09-24
Filing date: 2020-09-24
Publication date: 2022-09-13
Also published as: CA3154683A1; EP4034218A4; KR20220072853A; WO2021062032A1; EP4034218A1; WO2021062032A9; JP2022549325A

Abstract

Intravenous infusion catheter assemblies and methods of use are described herein. The catheter assembly may include an elongate body having a proximal end and a distal end, wherein an expandable occlusion element is disposed on the elongate catheter body. The catheter may include a first infusion lumen extending to a proximal infusion port located proximal of the occlusion element on the catheter body and a second infusion lumen extending to a distal infusion port. Some embodiments may use an aspiration lumen extending to at least one aspiration port. When the catheter is introduced into the vasculature of a patient, the aspiration port may be positioned in the superior vena cava or right atrium of the patient to draw blood, the distal infusion port positioned to direct a normal or high temperature fluid toward the heart of the patient, and the proximal infusion port positioned to create a flow of a low temperature fluid in the cerebral vasculature of the patient.

Description

Infusion catheter and method of use

RELATED APPLICATIONS

This application claims rights to U.S. provisional application No. 62/905104 filed on 24.9.2019, U.S. provisional application No. 62/947457 filed on 12.12.2019, U.S. provisional application No. 62/954363 filed on 27.12.2019, and U.S. provisional application No. 63/010601 filed on 15.4.2020, all of which are incorporated herein by reference.

Technical Field

The present disclosure relates generally to medical catheters, and more particularly to central venous catheters (central venous catheters).

Background

Interruption of blood flow to the brain can lead to permanent neurological dysfunction or brain death and occurs in many clinical settings. Interruption of cerebral blood flow occurs in cardiac surgery, such as stroke, cardiac arrest, carotid endarterectomy, and cardiac arrest. Despite best practices, the extensive neuroprotection provided to cardiac surgery patients by cryotherapy (or therapy) has not become readily deployable beyond this unique and limited environment. For stroke and sudden cardiac arrest patients, there is an urgent clinical need for a new immediate medical device and system to protect the brain and prevent disability and death.

Strokes occur due to occlusion (ischemic) or rupture (hemorrhagic) of the arteries supplying the brain. Ischemic strokes describe those strokes that are caused by an obstruction, usually an atherosclerotic plaque or a solid clot lodged in an artery. Brain damage from ischemic stroke occurs both due to initial obstruction and due to what is considered a secondary mechanism of "reperfusion injury," which can lead to additional damage upon reestablishment of blood flow. Existing treatments have focused only on restoring blood flow to brain tissue that is endangered, including recombinant tissue plasminogen activator (tPA) and thrombectomy (mechanical clot removal). Timely low temperature treatment is expected to alleviate ischemic injury and reperfusion injury. Such treatment would be applicable to stroke patients in a variety of settings, such as treatment during transport to a complex stroke center, during thrombectomy, and the like. Furthermore, therapeutic hypothermia, and optionally hypothermia, only in the brain may provide additional benefits, as cooling of the body can have deleterious effects. These adverse effects may include increased risk of pneumonia, increased coagulation dysfunction and bradycardia. Cooling the heart to around 32-33 ℃ or below is not considered safe because doing so may result in arrhythmias or complete cardiac arrest, as well as coagulation dysfunction. Selective cooling of the brain can reduce the detrimental effects of systemic cooling and allow deeper hypothermia levels to be safely achieved. An ideal solution would be to selectively cool the brain while leaving the body at or near normothermia.

Cardiopulmonary arrest (usually caused by cardiac arrest, but sometimes by respiratory failure in patients) is a medical emergency where loss of blood flow to the brain can lead to irreversible brain damage in as little as two minutes. Cardiopulmonary resuscitation (CPR) may be used to restore cardiopulmonary function and resuscitate the patient, but brain death and permanent neurological dysfunction may still occur. While extracorporeal membrane pulmonary oxygenation (ECMO) and the like is a small cardiopulmonary bypass that is theoretically effective if used immediately, this method requires time and sub-professionals to administer. The emergency situation of cardiac arrest is not conducive to this time and personnel intensive approach. Although some therapeutic hypothermia is employed during the recovery of cardiac arrest, this approach is too delayed and the depth of cooling is too shallow to substantially prevent nerve damage; furthermore, this sudden cooling down occurs systemically, which is associated with adverse consequences.

The ability to intervene with therapeutic hypothermia for neuroprotection can be expected to be fast, not interfere with workflow, and maintain physiological safety. Existing cryotechniques can be difficult to employ or achieve only shallow and systemic hypothermia, which limits the degree of neuroprotection provided by the treatment.

Thus, there is a need to improve neuroprotection in the event of interruption of cerebral blood flow; there is an opportunity to do this by converting the neuroprotective technology used in cardiac surgery (retrograde brain perfusion (RCP)). In particular, it would be desirable to provide a device and fluid delivery system to achieve low temperature RCP that is easy to implement, while maintaining whole body normothermia to allow deeper and more protective brain cooling. The improved central venous catheter and associated fluid delivery system may allow for cryogenic retrograde brain perfusion for neuroprotection in associated clinical indications.

Accordingly, described herein are methods, devices, and systems that enable point of care personnel in a hospital or other location to quickly protect the brain of a patient. Often, only physicians are able to place catheters in the central venous or arterial system. Therapeutic hypothermia through a catheter in the central vasculature can be performed in a hospital setting, but is not available in the extrahospital setting where most cardiac arrest and stroke occur. Existing systems do not allow EMTs, nurses, or other non-physician medical professionals to place a line in the central vasculature. These medical professionals come into contact with patients earlier outside hospitals, on-site, and during emergency transport.

Disclosure of Invention

Catheters and related fluid delivery systems may allow for hypothermic brain perfusion for neuroprotection in related clinical indications. Devices, related cooling systems, and methods of use that allow for such treatment may be explained herein. Furthermore, other methods of using such devices may be described in addition to brain cooling. Finally, an automated method of placing a device in the vasculature can be set forth. At least some of these objectives may be achieved by the invention described hereinafter.

According to one aspect of the present disclosure, an infusion catheter includes an elongate catheter body having one or more lumens extending longitudinally, such as a perfusion lumen (perfusion lumen), a drug delivery lumen, an inflation lumen, a temperature probe containment lumen, and the like, between a proximal end and a distal end. The elongate catheter body has at least one lateral port opening to an irrigation lumen, the proximal end of which is fluidly connectable to a fluid source to be delivered, typically including a proximal hub (hub) having an inlet port. An inflatable occlusion element, typically an inflatable balloon, is secured to an outer surface of the elongate catheter body, and at least one lateral port is located between the inflatable occlusion element and the proximal end or hub. The inflatable occlusion element can assume an inflated configuration and a deflated configuration, and typically includes a balloon structure fluidly connectable to a source of inflation fluid. According to various embodiments, the perfusion lumen of the present invention may be used to perfuse all types of media, including cryogenic and other preserved media, blood products, drugs, medicaments, and the like.

In some embodiments, an intravenous infusion catheter assembly may include an elongate catheter body having a proximal end and a distal end, with an expandable occlusion element disposed on the elongate catheter body. The catheter may include a first infusion lumen extending from the proximal end of the catheter body to a proximal infusion port located on the catheter body proximal to the occlusion element between the occlusion element and the proximal end of the catheter body. The catheter may also include a second infusion lumen extending from the proximal end of the catheter body to a distal infusion port located distal to the occlusion element on the catheter body. Some embodiments may use an aspiration lumen extending from the proximal end of the catheter body to at least one aspiration port positioned distal to the occlusion element on the catheter body. The proximal and distal infusion ports may be spaced relative to the occlusion element such that when the catheter is introduced into the vasculature of a patient, the aspiration port is located in the superior vena cava or right atrium of the patient to aspirate blood flowing through the catheter. A vena cava of a patient, a distal infusion port located in the superior vena cava or right atrium of the patient for directing a normothermic or hyperthermic fluid to the heart of the patient, and a proximal infusion port located in the internal jugular vein of the patient for generating retrograde flow of the cryogenic fluid in the cerebral vasculature of the patient.

In some embodiments, a method for treating a patient includes introducing a catheter into a venous vasculature of the patient to position a first outlet on the catheter at a location where blood flows into a right atrium of the patient and to position a second outlet on the catheter at a location where venous blood is drained from a cerebrovascular system. One or more medicaments, drugs, etc. may be delivered at a selected time in an antegrade direction through the first outlet of the catheter to the right atrium of the patient's heart. At other selected times, a preservative medium (e.g., a cryogenic fluid) may be delivered to the patient's cerebrovascular system in a retrograde direction through the second outlet of the catheter. In this manner, the catheter may be used to deliver drugs and other medications to a patient's heart in a manner similar to a central venous catheter, for example, in a hospital setting such as an intensive care unit. In the case of ischemic stroke, catheters may be used to deliver cooling or other preservation media to the cerebrovascular system of a patient over a period of time, in addition to delivering drugs, agents and fluids through their distal ports; after cryogenic treatment, which may be maintained for a period of time, the catheter may remain in the patient's vein and the additional lumen may be used to deliver drugs, drugs and fluids to the central venous system. In some embodiments, while the cooled fluid is delivered to the patient's cerebral vasculature in a retrograde direction, the heated fluid may be simultaneously delivered to the patient's heart to keep it warm.

For example, in some embodiments, the treatment may include creating an occlusion in a patient's internal jugular vein, wherein an expandable occlusion element is disposed on a catheter having a proximal end and a distal end, and then drawing blood from the patient's superior vena cava through a suction port into a suction lumen extending through the catheter. In some cases, the aspiration port may be located at the distal end of the catheter and proximal to the distal infusion port, in the right atrium or superior vena cava of the patient.

The treatment may further include delivering cryogenic fluid from the first heat exchange assembly through a first infusion lumen extending from the proximal end of the catheter body to the proximal infusion port and out of the proximal infusion port to create retrograde flow in the body of the patient. The cerebral vasculature and delivers the normothermic or hyperthermic fluid from, for example, the second heat exchange through a second infusion lumen extending from the proximal end of the catheter body to and out of the distal infusion port to direct the normothermic or hyperthermic fluid toward the heart of the patient. In some cases, the proximal infusion port at the proximal end of the catheter is located in the internal jugular vein of the patient and/or the distal infusion port at the distal end of the catheter is located in the right atrium or superior vena cava of the patient or near the junction of the vena cava of the patient.

In some embodiments, the catheter assembly may include one or more extracorporeal circuits to, for example, cool fluid for infusion and delivery to one organ and heat fluid for infusion and delivery to another organ. The conduit assembly may include one or more heat exchange assemblies fluidly connected to the conduit, which may include a heat exchanger, a pump, and a heat exchange circuit. The controller connected to the heat exchange assembly may be a controller that facilitates adjustment of, for example, the temperature and flow rate of the heat exchange assembly. In some embodiments, the controller may receive temperature sensor data and flow rate data, and using the processor and memory, may determine and transmit adjustments to be made by each heat exchange assembly.

For example, in some embodiments, the treatment may include creating an occlusion in an internal jugular vein of the patient, wherein the expandable occlusion element is disposed on a catheter having a proximal end and a distal end. The controller may receive a brain temperature based on measurements from the at least one skull temperature sensor, a heart temperature based on measurements from a temperature sensor positioned distal to the occlusion element on or within the catheter, a first flow rate from the first thermal exchange assembly indicative of a flow rate from the catheter into the patient's cerebral vasculature, and a second flow rate from the second thermal exchange assembly indicative of a flow rate from the catheter into the patient's heart. The controller may determine whether the heart temperature is below a second predetermined temperature and send a command to the second heat exchange assembly to increase the second flow rate if the heart temperature is below the second predetermined temperature. The controller may also determine whether the brain temperature is above a first predetermined temperature if the heart temperature is not below a second predetermined temperature, and in response to determining that the brain temperature is above the first predetermined temperature, send a command to the second heat exchange assembly to increase the second flow rate and send a command to the first heat exchange assembly to increase the first flow rate.

Drawings

Fig. 1A depicts an exemplary external view of a catheter according to some embodiments of the present disclosure;

fig. 1B depicts an exemplary external view of a catheter according to some embodiments of the present disclosure;

FIG. 2 is a detailed view of the balloon on the infusion catheter of the present invention shown in a deflated and inflated configuration;

fig. 3A depicts an exemplary cross-section of an infusion catheter of the present invention;

fig. 3B depicts an exemplary cross-section of a catheter with a temperature sensor attached to a stabilization wire, according to some embodiments of the present disclosure;

fig. 3C depicts an exemplary cross-section of a catheter having an insulating lumen, according to some embodiments of the present disclosure;

fig. 4 depicts an illustrative scenario for providing treatment with a catheter using a caged ball obturator in accordance with some embodiments of the present disclosure;

fig. 5 depicts an illustrative scenario for providing therapy through a catheter using a semi-cylindrical obturator in accordance with some embodiments of the present disclosure;

fig. 6 depicts an illustrative scenario of providing therapy using a catheter with a removable lumen, in accordance with some embodiments of the present disclosure;

fig. 7 depicts an illustrative scenario of providing therapy using a curved-tip catheter for inferior vena cava access, in accordance with some embodiments of the present disclosure;

Fig. 8 depicts an exemplary external view of a catheter with a non-occlusion balloon according to some embodiments of the present disclosure;

fig. 9 depicts an exemplary cross section of a catheter with a non-expanding, non-occlusive balloon according to some embodiments of the present disclosure;

fig. 10 depicts an exemplary cross-section of a catheter with an expanded non-occlusive balloon according to some embodiments of the present disclosure;

FIG. 11 depicts an exemplary external view of a catheter having an expandable element to facilitate aspiration, according to some embodiments of the present disclosure;

fig. 12 illustrates a system suitable for incorporation into a catheter in accordance with some embodiments of the present disclosure;

figure 13 illustrates a system using a controller adapted to be incorporated into a catheter according to some embodiments of the present disclosure;

FIG. 14 illustrates a system using an oxygenator and a controller suitable for incorporation into a catheter, in accordance with some embodiments of the present disclosure;

figure 15 illustrates a system using a controller incorporating a catheter according to some embodiments of the present disclosure;

fig. 16 illustrates a system using a controller incorporated for use with a patient, in accordance with some embodiments of the present disclosure;

fig. 17A illustrates a system using selective cooling and cardiac flashback, according to some embodiments of the present disclosure;

Fig. 17B illustrates a system for flashback of a patient's heart using selective cooling and a catheter, in accordance with some embodiments of the present disclosure;

fig. 18A is a block diagram of an illustrative system using a controller adapted to be incorporated into a catheter, in accordance with some embodiments of the present disclosure;

fig. 18B depicts an illustrative flow diagram of a process for regulating a therapy system using a controller and incorporating at least one heat exchange assembly, in accordance with some embodiments of the present disclosure;

fig. 18C depicts an illustrative flow diagram of a process for regulating a therapy system using a controller and incorporating two heat exchange assemblies in accordance with some embodiments of the present disclosure;

fig. 19 illustrates a system for selective treatment incorporating a catheter for a patient, in accordance with some embodiments of the present disclosure;

fig. 20 illustrates a system for antegrade treatment using a catheter through a patient's carotid artery, according to some embodiments of the present disclosure;

fig. 21 illustrates a system for antegrade treatment using a catheter through a radial artery of a patient according to some embodiments of the present disclosure;

fig. 22 illustrates a system for antegrade treatment using a catheter through a femoral artery of a patient according to some embodiments of the present disclosure;

figure 23 illustrates a system using antegrade treatment in which a catheter enters a carotid artery of a thrombectomy patient through a femoral artery, according to some embodiments of the present disclosure;

Fig. 24 illustrates a system using antegrade therapy with a catheter entering the brain of a thrombectomy patient through the femoral artery, according to some embodiments of the present disclosure;

fig. 25 illustrates a system using antegrade therapy in which a catheter is passed through a femoral artery over an occlusion into a patient's brain, according to some embodiments of the present disclosure;

fig. 26 illustrates a system for retrograde treatment using a catheter via a patient's internal jugular vein according to some embodiments of the present disclosure;

fig. 27 illustrates a system for retrograde therapy using a catheter via a femoral vein of a patient according to some embodiments of the present disclosure;

fig. 28 illustrates a system for retrograde therapy using a catheter via the subclavian vein of a patient according to some embodiments of the present disclosure;

fig. 29 illustrates a system for retrograde therapy using a catheter via the cephalic vein of a patient according to some embodiments of the present disclosure;

figure 30 illustrates a system using retrograde therapy in which a catheter is passed through the femoral vein and into the brain of a patient, according to some embodiments of the present disclosure;

fig. 31 illustrates a system using retrograde therapy using saline infusion, with a catheter via the internal jugular vein of a patient, according to some embodiments of the present disclosure;

fig. 32 illustrates a system using retrograde therapy using saline infusion, with a catheter aspirating via the patient's internal jugular vein and from the transfemoral vein, according to some embodiments of the present disclosure;

Figure 33 illustrates a system using retrograde therapy using saline infusion, with a catheter aspirating through and from the internal jugular vein of a patient, according to some embodiments of the present disclosure;

fig. 34 illustrates a system using retrograde therapy using saline infusion, where the catheter uses reverse flow to remove clots, according to some embodiments of the present disclosure;

fig. 35 illustrates a system using retrograde therapy using saline infusion, where the catheter uses retrograde flow to remove clots during embolectomy, according to some embodiments of the present disclosure;

fig. 36 illustrates a system using retrograde therapy using saline infusion, where the catheter is cooled using retrograde flow during embolectomy, according to some embodiments of the present disclosure;

fig. 37 illustrates a system using retrograde therapy using saline infusion, with a catheter via the internal jugular vein of a patient, according to some embodiments of the present disclosure;

fig. 38 illustrates a system for retrograde therapy in which a catheter is used to deliver a drug to the brain, according to some embodiments of the present disclosure;

fig. 39 illustrates a system for treatment in which a catheter is configured to aspirate fluid in the internal jugular vein of a patient and return fluid in the internal jugular vein, according to some embodiments of the present disclosure;

Fig. 40 illustrates a system for retrograde therapy in which the catheter is configured to aspirate fluid in the femoral vein and return fluid in the internal jugular vein of a patient, according to some embodiments of the present disclosure;

fig. 41 illustrates a system for retrograde therapy in which the catheter is configured to aspirate fluid in the subclavian vein and return fluid in the internal jugular vein of a patient, according to some embodiments of the present disclosure;

fig. 42 illustrates a system for retrograde therapy in which fluid is drawn in the cephalic vein and returned in the internal jugular vein of a patient, in accordance with some embodiments of the present disclosure;

fig. 43 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a femoral vein and return fluid in a cerebral vein of a patient, according to some embodiments of the present disclosure;

fig. 44 illustrates a system for antegrade treatment in accordance with some embodiments of the present disclosure, wherein the catheter is configured to aspirate fluid in the femoral vein of the patient and return the fluid into the cerebral artery;

fig. 45 illustrates a system for antegrade treatment in accordance with some embodiments of the present disclosure, wherein the catheter is configured to aspirate fluid in the femoral vein of the patient and return the fluid into the carotid artery;

fig. 46 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in the femoral vein of a patient and to return fluid in the internal jugular vein, according to some embodiments of the present disclosure;

Fig. 47 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a femoral artery of a patient and to return fluid in a femoral vein, according to some embodiments of the present disclosure;

fig. 48 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in the femoral vein of a patient and to return fluid in the subclavian vein, according to some embodiments of the present disclosure;

fig. 49 illustrates a system for antegrade treatment in accordance with some embodiments of the present disclosure, wherein the catheter is configured to aspirate a fluid in a femoral vein of a patient and to return the fluid into a carotid artery;

fig. 50 illustrates a system for antegrade treatment in accordance with some embodiments of the present disclosure, wherein the catheter is configured to aspirate a fluid in a femoral vein of a patient and to return the fluid in a radial artery;

fig. 51 illustrates a system for antegrade treatment, in accordance with some embodiments of the present disclosure, wherein a catheter is configured to suction a fluid in a femoral artery of a patient and to return the fluid in a radial artery;

fig. 52 illustrates a system for antegrade treatment in accordance with some embodiments of the present disclosure, wherein the catheter is configured to draw fluid from any vein of a patient and to return the fluid into the femoral artery;

Fig. 53 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in the femoral vein of a patient and to return fluid to the internal jugular vein, in accordance with some embodiments of the present disclosure;

fig. 54 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in the cephalic vein of a patient and to return fluid in the internal jugular vein, according to some embodiments of the present disclosure;

fig. 55 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a patient's carotid artery and to return fluid into the internal jugular vein, according to some embodiments of the present disclosure;

figure 56A illustrates a system for antegrade closed loop therapy according to some embodiments of the present disclosure;

figure 56B illustrates a system for retrograde closed loop therapy, according to some embodiments of the present disclosure;

figure 57 illustrates a system for treatment used in a thrombectomy procedure, according to some embodiments of the present disclosure;

fig. 58 illustrates a system for treatment in which the catheter is configured as an intrabody heat exchanger, according to some embodiments of the present disclosure;

fig. 59A illustrates an embodiment of a catheter with an impeller in accordance with some embodiments of the present disclosure;

Fig. 59B illustrates an embodiment of a catheter with a propeller according to some embodiments of the present disclosure;

fig. 60 illustrates a system for treatment in which a catheter is configured for limb perfusion, according to some embodiments of the present disclosure;

fig. 61 illustrates a system for treatment with a catheter during carotid endarterectomy, in accordance with some embodiments of the present disclosure;

figure 62 illustrates a system for automated catheter placement according to some embodiments of the present disclosure;

FIG. 63 illustrates a system for automated placement of a catheter according to some embodiments of the present disclosure;

fig. 64 illustrates a system for gastric lavage incorporated therapy for central temperature management according to some embodiments of the present disclosure;

figure 65 illustrates a system for treatment incorporating gastric lavage for central temperature management and an outer sheath, in accordance with some embodiments of the present disclosure;

fig. 66 depicts an exemplary external view of an insulated guide catheter, according to some embodiments of the present disclosure;

fig. 67 depicts an exemplary cross-sectional view of an insulated guide catheter, according to some embodiments of the present disclosure;

fig. 68 depicts an exemplary cross-sectional view of an insulated guide catheter, according to some embodiments of the present disclosure;

figure 69 illustrates a system for treatment incorporating an insulated guide catheter, according to some embodiments of the present disclosure;

Figure 70 illustrates a system for therapy incorporating an insulated guide catheter and a cooling console, according to some embodiments of the present disclosure;

FIG. 71 is a side view of a first embodiment of an intravenous infusion catheter constructed in accordance with the principles of the present invention, in accordance with some embodiments of the present disclosure;

fig. 72 is a cross-sectional view of the iv catheter of fig. 71, according to some embodiments of the present disclosure;

fig. 73 is a front view of the iv catheter of fig. 71, according to some embodiments of the present disclosure;

fig. 74 is a side of an intravenous infusion catheter including a balloon in an inflated configuration according to one embodiment in accordance with some embodiments of the present disclosure;

fig. 75 is a cross-sectional view of the iv catheter of fig. 74, according to some embodiments of the present disclosure;

fig. 76 is a front view of the iv catheter of fig. 74, according to some embodiments of the present disclosure;

figure 77 illustrates an intravenous infusion catheter installed in an internal jugular vein, according to embodiments, in accordance with some embodiments of the present disclosure;

fig. 78 illustrates an intravenous infusion catheter including a catheter for delivering inflation fluid to a balloon according to embodiments, the balloon in a deflated state, in accordance with some embodiments of the present disclosure;

fig. 79 illustrates the iv catheter of fig. 78 with the balloon in an inflated state, according to some embodiments of the present disclosure;

Fig. 80 illustrates a catheter including only an outer balloon and configured to deliver two fluids simultaneously in opposite directions, the outer balloon being in a deflated state, according to some embodiments of the present disclosure;

fig 81 illustrates the catheter of fig 80 with the outer balloon in an inflated state according to some embodiments of the present disclosure;

fig. 82A is a side view of an embodiment of an intravenous infusion catheter in accordance with the principles of the present invention, in accordance with some embodiments of the present disclosure;

fig. 82B illustrates an alternative hub and connector assembly for the catheter of fig. 82 in accordance with some embodiments of the present disclosure;

fig. 83A is a cross-sectional view taken along line 83A of fig. 82A, according to some embodiments of the present disclosure;

fig. 83B is a cross-sectional view taken along line 83B of fig. 82A, according to some embodiments of the present disclosure;

fig. 83C is a cross-sectional view taken along line 83C of fig. 82A, according to some embodiments of the present disclosure;

fig. 83D is a cross-sectional view taken along line 83D of fig. 82A, according to some embodiments of the present disclosure;

fig. 84A illustrates an external occlusion element having an alternative configuration in accordance with some embodiments of the disclosure;

fig. 84B illustrates an outer occlusion element having an alternative configuration according to some embodiments of the present disclosure;

fig. 84C illustrates an outer occlusion element having an alternative configuration according to some embodiments of the present disclosure;

Figure 85 illustrates the venous perfusion catheter of figure 82A placed in the venous vasculature of a patient according to some embodiments of the present disclosure;

fig. 86 is a block diagram illustrating components of a therapy system according to some embodiments of the present disclosure;

figure 87A illustrates an embodiment of an intravenous infusion catheter, in accordance with some embodiments of the present disclosure;

fig. 87B illustrates an embodiment of an intravenous perfusion catheter in accordance with some embodiments of the present disclosure;

fig. 88A is a cross-sectional view taken along line 88A of fig. 87A according to some embodiments of the present disclosure;

fig. 88B is a cross-sectional view taken along line 88B of fig. 87A, according to some embodiments of the present disclosure;

FIG. 88C is a cross-sectional view taken along line 88C of FIG. 87A, according to some embodiments of the present disclosure;

fig. 88D is a cross-sectional view taken along line 88D of fig. 87A, according to some embodiments of the present disclosure;

fig. 89A is a cross-sectional view taken along line 89A of fig. 87B, in accordance with some embodiments of the present disclosure;

fig. 89B is a cross-sectional view taken along line 89B of fig. 87B, in accordance with some embodiments of the present disclosure;

figure 90A illustrates an embodiment of an intravenous infusion catheter, in accordance with some embodiments of the present disclosure;

figure 90B illustrates an embodiment of an intravenous infusion catheter, in accordance with some embodiments of the present disclosure;

Fig. 91A illustrates an embodiment of an intravenous infusion catheter in accordance with some embodiments of the present disclosure; and

fig. 91B illustrates an embodiment of an intravenous perfusion catheter in accordance with some embodiments of the present disclosure.

Detailed Description

It is understood that the disclosure herein is partially described by their associated drawing(s). The drawings are intended to depict potential embodiments. As such, some embodiments typically appear as part of a five-lumen or six-lumen catheter, however, it is understood that the disclosure may be incorporated into catheters having a greater or lesser number of lumens, as appropriate. Similarly, the magnified images included for viewing details typically only show the lumens necessary for the relevant disclosure; for example, a cross-section may include one or more lumens other than the one depicted in cross-section in the figures herein, as appropriate.

It is understood that within the present disclosure, a proximal port may be referred to as an infusion port, and vice versa. Additionally, objects described as infusion lumens may be described as common infusion/medication lumens. An object described as an infusion lumen or port is synonymous with an object described as an infusion lumen or infusion port, respectively. An object described as an infusion lumen may also refer to an infusion port, or an infusion lumen. Similarly, one or more of the distal port and the suction port may refer to the same feature. The object described as an infusion lumen may be a lumen that is used only to deliver fluid through an infusion port, or may be a lumen that may be used to deliver fluid through one or more outlet ports (potentially, a proximal infusion port in some configurations, and a distal port in other configurations). The expandable obturator (occluder) may also be described as an occlusion element, an expandable occlusion element, and includes an occlusion balloon or balloon as described in some embodiments. It is understood that the language including catheter, device, infusion catheter, elongate catheter body, therapy delivery (therapy delivery) device, fluid delivery device, access catheter may all refer to the same device: the device(s) described in detail below. An object described as a therapeutic fluid or a therapeutic medium may also be described as an infusion fluid, perfusion fluid, perfusate, or pharmaceutical agent or medium. Additionally, the cooling system, the treatment circulation system, the treatment delivery device may also all refer to the same system.

1.1 aspects of an infusion catheter device (see FIGS. 1-3)

Fig. 1A depicts an exemplary external view of a catheter according to some embodiments of the present disclosure. In some embodiments, an infusion catheter may include an elongate catheter body 202 having one or more lumens extending longitudinally between a proximal end 206 and a distal end 204, and an expandable occlusion element is provided, as disclosed herein. An infusion catheter may also be referred to as an infusion cannula. The elongate catheter body 202 can have at least one port, which can be a lateral port, open to the infusion lumen, wherein the proximal end 206 of the infusion lumen can be fluidly connected to a fluid source to be delivered, which typically includes a proximal hub 218 having an inlet port. The one or more lumens may include lumens for infusion, aspiration, drug delivery, balloon inflation, temperature measurement, pressure measurement, lumens for central venous pressure measurement, and the like. Fig. 3 depicts an exemplary cross-section of an infusion catheter of the present invention. As labeled herein, the cross-section of the body of the catheter is an example of a possible lumen geometry, but the shape may be semi-circular, elliptical, kidney-shaped, or some other shape(s) to maximize flow rate and minimize risk of lumen collapse. The catheter may contain any number of combinations of these lumens. An expandable occlusion element (typically an inflatable balloon) may be affixed to the outer surface of the elongate catheter body 202, and at least one lateral port may be located between the expandable occlusion element and the proximal end 206 or hub 218. The expandable occlusion element is capable of assuming an expanded configuration and an unexpanded configuration, typically including a balloon structure fluidly connectable to a source of inflation fluid. The device may be placed in a blood vessel (vein or artery) of a patient and may be used to deliver therapy. The infusion lumen can be used to infuse all types of media including cryogenic media, normothermic media, hyperthermic media and other preserved media, blood products, drugs, medicaments, autologous blood, and the like.

One or more temperature sensors may be disposed in a lumen (such as an aspiration, infusion, balloon, or pressure measurement lumen) or may be embedded in the material of the device. The at least one aspiration lumen 216 port may be located distal to the expandable obturator and the at least one infusion lumen port may be located proximal to the expandable obturator. There may be additional one or more infusion lumen ports located distal to the aspiration lumen 216 port. An infusion lumen with one or more ports located proximal to the balloon may be used to infuse a cooled cryogenic medium at a temperature below the body temperature of the patient. An infusion port located distal to the expandable obturator may be used to infuse a normothermic medium at a temperature at or near the temperature of the patient's body or a hyperthermic medium at a temperature above the body temperature of the patient. One or more aspiration ports 238 may be located distal to the expandable obturator, while one or more infusion ports may be located between the expandable occlusion element and the inlet. The one or more suction ports 238 may be disposed only distal to the balloon, such that in the event of a strong suction, if the catheter body 202 distal to the expansible obturator is in contact with the vessel wall to be suctioned, the suction port 238 closest to the expansible obturator may remain open because it may not become suctioned to the vessel wall due to the expansible obturator. One or more temperature sensors may be located on the catheter body 202. A temperature sensor disposed on or in the body of the catheter near the lateral suction port 238 may inform the knowledge of the heart or brain temperature based on the blood flow in the body past the temperature sensor at that location. A temperature sensor disposed near the distal end 204 of the catheter, on or in the body of the catheter, may inform the knowledge of the heart temperature based on the blood flow past the sensor at that location. The temperature sensor may be threaded down its own lumen into the body of the catheter or, as in the primary embodiment discussed herein, may reside in another lumen of the catheter (such as a balloon inflation lumen) in order to save space in the catheter body 202 and minimize the overall size of the device.

The entire body of the elongate catheter or portions thereof may contain reinforcement to prevent collapse of the lumen; in particular, the aspiration lumen 216 may be reinforced to prevent potential collapse due to aspiration. The exterior of the infusion catheter may be reinforced to provide reinforcement to all lumens within the interior, the lumens themselves may be reinforced individually, or it is possible to use some combination of these to reinforce the tubing. Suction may be applied using a dedicated pump, an associated system or standard extracorporeal membrane oxygenation (ECMO) or heart-lung machine (e.g., a temperature modulation system such as discussed in this document). The reinforced body may be reinforced using coiled material, such as stainless steel, to act as a reinforcement. The coiled reinforcement may provide improved hoop strength and kink resistance while maintaining flexibility of the device. Braided reinforcements may also be used to reinforce the duct. The proximal portion of the lumen between the fluid connector and the mounting hub 218 may also be reinforced. In some embodiments, at least one hypotube (hypotube) may be used as a stiffener.

Fig. 1B depicts an exemplary external view of a catheter according to some embodiments of the present disclosure. In some embodiments such as depicted in fig. 1B, the iv catheter assembly may include an elongate catheter body 202, the elongate catheter body 202 having a proximal end 206 and a distal end 204, wherein an expandable occlusion element 244 is disposed on the elongate catheter body 202. The catheter may include a first infusion lumen extending from the proximal end 206 of the catheter body 202 to a proximal infusion port on the catheter body 202 located proximal of the occlusion element between the occlusion element and the proximal end 206 of the catheter body 202. The catheter may further include a second infusion lumen extending from the proximal end 206 of the catheter body 202 to a distal infusion port located on the catheter body 202 distal to the occlusion element. Some embodiments may use an aspiration lumen 216, the aspiration lumen 216 extending from the proximal end 206 of the catheter body 202 to at least one aspiration port 238 located on the catheter body 202 distal to the occlusion element. The proximal and distal infusion ports may be spaced relative to the occlusion element such that when the catheter is introduced into the patient's vasculature, the aspiration port 238 is positioned in the patient's superior vena cava or right atrium to draw blood flowing through the patient's vena cava, the distal infusion port is positioned in the patient's superior vena cava or right atrium to direct a normothermic or hyperthermic fluid toward the patient's heart, and the proximal infusion port is positioned in the patient's internal jugular vein to create retrograde flow of the cryogenic fluid in the patient's cerebral vasculature.

1.1.2 temperature sensor attached to stabilizing wire (see FIG. 3B)

Fig. 3B depicts an exemplary cross section of a catheter with a temperature sensor attached to a stabilization wire according to some embodiments of the present disclosure. In some embodiments, the enhancer may be comprised of a wire that can communicate with a temperature sensor. As depicted and described above, the wire may act as a coiled reinforcement to provide improved hoop strength and kink resistance while maintaining flexibility of the device. The wire may take a variety of shapes or configurations, such as a braided shape.

One or more temperature sensors may be used to measure the temperature at or near the distal end 204 of the device. In a particular example, the distal end 204 is located at or near an atrial boundary, allowing the temperature readings to serve as a measure of the temperature near the heart or allowing the temperature of the heart itself to be measured. One or more additional temperature sensors may be located in the infusion catheter, allowing temperature to be measured at other points of the device. In a potential embodiment, a temperature sensor may be located at or near the suction port 238 of the catheter, allowing the temperature of the blood at that location to be known at or near the superior vena cava at or near the right and left brachiocephalic vein anastomoses. One or more pressure sensing ports may be located proximal to the expandable obturator and may be used to measure the pressure generated by the outward flow of fluid from one or more of the infusion lumens. Fluid may be aspirated outwardly from the one or more aspiration lumen 216 ports and infused into the one or more infusion lumen ports after passing through the extracorporeal system, where the fluid medium may be temperature modulated, oxygenated, or both. The one or more infusion lumens may be in fluid communication with a port located proximal to the expandable obturator and may be referred to as a proximal infusion lumen, or in some instances, a cooling lumen, as it can be used to direct a cooled medium retrograde toward the brain. One or more infusion lumens may be in fluid communication with a port located distal to the expandable obturator and may be referred to as a distal infusion lumen, or in some cases, an anti-hyperthermia lumen, as the lumen may direct the warmed medium anterogradely toward the heart. The distal infusion lumen may infuse a normothermic or hyperthermic medium that may warm or maintain the temperature of the heart when the device is being used to selectively cool the brain in a human patient. This may prevent the heart, body, or both from reaching temperatures that are considered dangerously low. In other configurations, the one or more infusion ports may be located distal to the expandable occlusion element, while the aspiration lumen 216 may be located proximal to the expandable occlusion element. The one or more infusion ports and the one or more aspiration ports 238 may have luer fluid connectors or barb fluid connectors at their proximal ends 206.

In some embodiments, an expandable occlusion element (typically an inflatable balloon) may be affixed to the outer surface of the elongate catheter body 202. The expandable occlusion element is capable of assuming an expanded configuration and a collapsed configuration, typically including a balloon structure fluidly connectable to a source of inflation fluid. In some embodiments, the expandable occlusion element may be a sheath balloon, such that the balloon may be flush with the body of the catheter in its collapsed state, thereby allowing for smooth insertion into the vasculature using the Seldinger technique, potentially under certain use conditions. In some examples, the unexpanded diameter of the sheath balloon may be greater than 30% of the outer diameter dimension of the infusion catheter. For example, if the infusion catheter has an outer diameter dimension of 3mm, the unexpanded diameter of the sheath balloon may be less than 3.9 mm. This may be advantageous when the device is placed in a patient's blood vessel, to allow the device to slide through a small orifice without damaging the insertion site, and may minimize the risk of flashback. To accomplish this, the expandable obturator may be a balloon made of polyurethane, Pebax, latex or a similarly expandable material that is capable of expanding from less than 30% greater than the outer diameter of the iv catheter in its collapsed state to 300% or greater of the outer diameter of the iv catheter in its expanded state. For example, if the outer diameter of the infusion catheter is 3mm, the unexpanded diameter of the balloon may be less than 3.9mm, and the balloon may have an expanded diameter of 11.7mm or greater. The balloon may be made using an extrusion process that produces a thin-walled tube. In some examples, the expandable occlusion element may be positioned such that the balloon inflation lumen is capable of delivering a fluid to inflate the expandable occlusion element. The expandable occlusion element may be thermally bonded to the body of the device at a point where it is positioned over the balloon inflation lumen, may be secured using a UV-cured adhesive, secured using another type of adhesive, secured using a heat-shrinkable tubing, or some combination thereof, such that it covers the balloon inflation lumen. The balloon inflation lumen may have one or more outlet ports located underneath the balloon. To inflate the expandable occlusion element, a fluid (such as air, water, a lens, a medical contrast agent, or the like) may be infused through the balloon inflation lumen. The expandable obturator may be positioned such that it remains located in the internal jugular vein and, when placed in a human body, occludes the internal jugular vein when inflated, as opposed to occluding the superior vena cava, subclavian vein, brachiocephalic vein, or other similar venous structures. This may allow flow in the vessel to be occluded above the superior vena cava and brachiocephalic veins, such that any infusion fluid administered proximal to the balloon may produce retrograde perfusion of the head, rather than of the arm and head.

1.1.2.1 visualization of Expandable obturator (see FIG. 2)

Fig. 2 is a detailed view of the balloon on the infusion catheter of the present invention shown in a deflated configuration and an inflated configuration. In potential embodiments, it may be advantageous to easily visualize the expansion of the expandable obturator and to visualize when the expandable obturator is preventing flow in a blood vessel. The elongated catheter may be placed under ultrasound guidance using the Seldinger technique. Inflation of the expandable obturator may use a stirred solution, such that gas bubbles are dispersed in the fluid. As such, the stirred solution may be visible under ultrasound visualization and may act as an indicator that the obturator may have reached its expanded state. The stirred solution may be achieved by connecting two syringes and rapidly transferring fluid between them via a three-way stopcock. Similarly, a special syringe that introduces some gas into the fluid entering the balloon may be used. Likewise, the agitated solution may be contained by a special luer lock located at the proximal end 206 of the balloon inflation lumen, which would allow air to flow in to similarly agitate the fluid flowing into the balloon.

In some embodiments, the infusion catheter device may have an antimicrobial coating. In some examples, the antimicrobial coating may be used to reduce the risk of infection. The coating may also be lubricious to allow the device to slide smoothly when placed in the orifice. In some examples, the coating may include a silver-based antimicrobial agent. The coating may be applied only to the portion of the device intended to pass through an orifice, such as a hole in the skin of a human body, in order to place a medical device into a blood vessel.

In some embodiments, the device may have mounting features. The mounting features may allow the device to be secured to external objects, such as the skin of a patient who may have the device in their vasculature. In some examples, the mounting feature may be a small aperture that allows sutures or other similar mounting material to pass through the aperture and be tethered downward to secure the device to an external object. In other examples, the mounting feature may be an adhesive capable of adhering to an external object. The mounting features may be added to the device by additional manufacturing processes, such as an overmolding process or the mounting of components made by additive manufacturing. The mounting features may be made of a flexible material such that they conform to external objects during mounting.

In some embodiments, the infusion catheter may be placed in the orifice using an insertion device. The insertion device may be an insertion sheath and may have a higher stiffness than the body of the infusion catheter. The insertion device may help expand the insertion orifice and may have a larger diameter than the infusion catheter if the infusion catheter is circular in shape. If the cross-sectional shape of the infusion catheter is a shape other than circular, the insertion device may be the same cross-sectional shape as the infusion catheter and may be the same size or slightly larger. The infusion catheter may be placed into an orifice (such as an orifice in human skin) by screwing it through an insertion device. The insertion device may be made of a peel-off material so that the insertion device can be peeled off and removed once the infusion catheter has been inserted into the orifice.

In some examples, the conduit may be insulated. Insulation may be used to maintain the temperature of the fluid passing through the device, such as the warming of a cool fluid in the device. Each lumen of the device may be insulated individually, or one or more lumens may be insulated in any combination. In some embodiments, a lumen with a warm fluid, which may be a normothermic or warmed medium (such as blood), may be immediately adjacent to a lumen with a cold fluid, which may be a cooled medium (such as blood). In these embodiments, insulation may help maintain the lumens at their desired temperatures or at least reduce temperature fluctuations. In one embodiment, a lumen carrying a warmer fluid (such as a flashback lumen carrying normothermic to hyperthermic 36-40 ℃ blood) can be partially or completely enclosed by an outer lumen that may be carrying an insulating medium to help prevent heat transfer from a lumen that can have a lower desired temperature (such as, for example, a proximal perfusion or cooling lumen carrying normothermic 0-36 ℃ blood).

1.1.3 insulation of infusion catheters (see FIG. 3C)

Fig. 3C depicts an exemplary cross-section of a catheter having an insulating lumen, in some embodiments, the lumen carrying the colder fluid may be partially or completely enclosed by an outer lumen that may be carrying an insulating medium, according to some embodiments of the present disclosure. The labeled embodiments have one lumen, the perfusion lumen, insulated, but in other embodiments, any of the lumens may be insulated. Potentially circulating fluids or solid materials may be used for insulation. In some embodiments, the lumen interior may be coated with an insulating material (such as rubber or foam) to help prevent heat transfer. In other embodiments, a cylindrical sheath made of an insulating material (such as rubber or foam) may be inserted into one or more lumens to help minimize heat transfer within the device.

In some instances, a guidewire (guidewire) may be capable of passing through one or more lumens of the device. The guidewire may allow the device to be more easily placed in a patient's blood vessel. The guidewire may be flexible or rigid depending on the intended placement location of the device. The guidewire may allow the device to be placed using the Seldinger technique. The guidewire may pass through a lumen of the device, and the lumen through which the guidewire passes may be the lumen having the most distal exit port. The guidewire may be threaded through a lumen having a soft tip located on its distal end 204.

In some embodiments, one or more infusion lumens may have one or more ports disposed proximal to the expandable occlusion element. In such instances, all or some of the infused fluid may be delivered through one or more proximal infusion ports, and the expandable occlusion element may be used to direct flow in an antegrade (if unexpanded) or retrograde (if expanded) direction, as described in more detail herein.

In other embodiments, the one or more infusion lumens may have one or more ports disposed proximal to the expandable occlusion element and one or more ports disposed distal to the expandable occlusion element. In such instances, the infusion catheter typically further includes a shunt (such as an internal valve, trap door, slip fit tube) or other occlusion structure disposed in the infusion lumen at a longitudinal location between the at least one lateral port proximal to the outer expandable occlusion element and the open distal end 204 and/or the lateral port distal to the outer expandable occlusion element. In a first configuration, the shunt may block or redirect flow from the proximal outlet port such that the flow is released from the port distal to the outer expandable occlusion element. In a second configuration, the shunt may block or redirect flow from the distal outlet port such that the flow is released from the port proximal to the outer expandable occlusion element. A tube with a slip fit in the infusion lumen may be used to selectively open and close the outlet port.

In some embodiments, the device may have a lumen for measuring pressure proximal to the expandable occlusion element, pressure lumen 217. The lumen may have a female luer lock connector located on its proximal end 206 so that it may be connected to a pressure monitoring kit or device. The lumen may also be a lumen in which one or more of the one or more temperature sensors are placed.

In other embodiments, one or more sensors (potentially including but not limited to temperature, pressure, or flow rate sensors, or some combination thereof) may be integrated into the body of the catheter so that measurements of fluid flowing through the catheter or through the vasculature may be evaluated. In some instances, a temperature sensor may be disposed distal to the expandable obturator and a pressure sensor may be present proximal to the expandable obturator. In some examples, the temperature sensor may be a thermocouple or a thermistor. A pressure sensor may be located outside the device and may be attached to the inlet hub 218 to measure the fluid pressure in the lumen associated with the inlet hub 218. The pressure sensor may be a strain gauge, or the pressure monitoring lumen may be connected to a pressure monitoring system or device to measure pressure. The proximal end 206 of the sensor (such as a temperature sensor) may be an electrical connector that may allow the sensor to communicate with other systems, such as the temperature modulation system described herein. The electrical connector may have, for example, two pins.

In some embodiments, the distal tip 205 of the device may be tapered, soft, or some combination thereof to reduce the likelihood of damage to blood vessels in the body. The distal tip 205 may be made of the same material as the catheter body 202, but may have a lower durometer. In some instances, the tip may not be part of the device, but may be part of an insert that is inserted into a lumen having an exit at the distal tip 205 of the device. A tipped insert may protrude from the distal tip 205 of the device and may allow for easy insertion without causing damage to the body's blood vessels. Once the device has been placed in the blood vessel, the distal insert may be removed.

The body of the device may have location markings indicating how far into the orifice the device is insertable, such as a human fluid vessel. These location markers 207 may be radiopaque. These position markers 207 may be made of ink and may be screen printed or pad printed onto the device. Additional markers may be placed on the proximal lumen or female luer connector to indicate the flow rate for which the lumen is certified for adaptation. In some embodiments, the position marker may be positioned on or proximally adjacent to the catheter body 202 at one or more lateral ports (such as the aspiration port 238), proximal infusion port, or distal infusion port. In some embodiments, a position marker may be positioned on distal tip 205. Radiopaque markers may be placed on the device to allow X-ray and fluoroscopy to be used to image the device. In some cases, an ultrasound-opaque marker may be used.

In some instances, the device may include a leakage prevention member, such as a grommet, for plugging a hole or aperture through which the device can potentially be inserted into a vessel wall. The leak-resistant member may be made of rubber, silicone, polyurethane, or other similar flexible material. The leakage prevention means may be used to prevent leakage after the device has been placed into the orifice of a blood vessel containing fluid, especially when the blood vessel is experiencing elevated pressure compared to its normal condition.

In at least one embodiment, the infusion catheter may be provided in a kit (such as a single use kit). A kit may include at least one of the perfusion catheters of the present disclosure. The kit may optionally include at least one syringe, at least one needle, at least one suture, sterile dressings to be used by a doctor or other medical professional, sterile dressings for a patient, face masks to be used by a doctor or other medical professional, hair nets for a doctor or other medical professional, local anesthetics, skin cleansers, at least one scalpel, at least one transduction probe, at least one guide wire, at least one skin dilator, at least one medical napkin, at least one needle driver, and at least one needle safety station for used needles and other sharps. The kit may also include a cap, such as with a luer connector and a lumen clip, to occlude one or more lumens of the device that may be used with an infusion catheter. The kit may include instructions regarding the use of the device. The kit may be aseptically packaged and may be contained in a vacuum formed tray. The outer package may be made of plastic, paper, cardboard, or some combination thereof.

1.2 infusion catheters

In an embodiment, an infusion catheter may be used to achieve low temperatures (hypothermia) in the brain while maintaining normothermic or near normothermic temperatures in the body, where the brain is targeted for deep, rapid cooling. Infusion catheters may also be used to deliver oxygenated blood to the brain. The cooling system may consist of a catheter and an extracorporeal cooling, warming and oxygenation system. The infusion catheter may be placed in the neck Internal (IJ) vein of the patient. Here, it may draw blood from the patient through the suction lumen 216 of the device, circulate it extracorporeally through a modulation circuit that may include cooling, oxygenation, warming, or some combination thereof, and deliver the conditioned blood back to the body; some of the blood that is drawn before the conditioned blood is returned to the body through its respective lumen may be conditioned in one way while another portion is conditioned in another way. The cooled blood, which may also be oxygenated, may be directed toward the patient's brain via a proximal perfusion lumen leading proximally of the occlusion element, thereby flowing retrograde. The warmed blood, which may also be oxygenated, may be directed toward the patient's heart via a distal perfusion lumen leading distally of the occlusion element, flowing anterograde.

In some embodiments, a sterile, single-use intravascular five-fluid lumen occlusion balloon catheter and may be made with proprietary multi-lumen tubing and balloons. The proprietary conduit may be a multi-lumen conduit and may be the portion of the device intended to be inserted into the vasculature. The balloon may be a sheath balloon and may be positioned as flush as possible with the device when it is not inflated. The balloon may be thermally bonded, affixed with a UV cure or other adhesive, affixed using heat shrinking, or some combination thereof to secure it to the outer surface of the multi-lumen tubing. The device may contain a temperature sensor located near the distal end 204 of the device that measures the temperature at or near the heart, or may be used to measure the temperature of fluid in the vein. The temperature sensor may have a proximal portion that terminates in an electrical connector to allow it to interface with an external system. The fluid lumens may have fluid connectors on the proximal portion of the lumen to allow them to interface with external systems. The catheter may have a mounting hub 218, the mounting hub 218 connecting the proximal fluid lumen and the proximal portion of the temperature sensor to the multi-lumen intravascular extrudate. The tip of the device may be tapered, soft, or both tapered and soft, and/or have a lower durometer than the extrudate to prevent damage to the vessel. Each lumen may be in fluid communication with its respective outlet(s).

The device may contain a lumen, balloon inflation lumen, in communication with one or more ports thereof located beneath the bonded sheath balloon. The one or more ports may be cut or incised into a side of the balloon inflation lumen of the multi-lumen conduit that is located below the balloon bottom, and the lumen may be sealed distal to the one or more outlets. The balloon inflation lumen may contain a temperature sensor. A balloon inflation lumen may be used to inflate the balloon.

The device may contain a lumen in communication with its port or ports located proximal to the balloon, pressure lumen 217. One or more ports may be cut or cut into a side of the pressure lumen 217 of the multi-lumen tubing proximal to the balloon, and the lumen may be sealed distal to the one or more outlets. The pressure lumen 217 may contain a temperature sensor. The pressure lumen 217 may be used to measure pressure generated by flow through the proximal infusion lumen or pressure generated by the subject's venous system, or a combination thereof.

The device may include a lumen, suction lumen 216, capable of suctioning blood when attached to a suction source. The one or more ports may be cut or incised into a side of the aspiration lumen 216 of the multi-lumen tubing distal to the balloon, and the aspiration lumen 216 may be sealed distal to the one or more ports. One or more outlets/inlets of the lumen may be located at the distal tip 205 of the catheter. It can fit a 0.038 inch (about 0.97mm) diameter guidewire to facilitate device placement. The distal inlet/outlet of the lumen may be a tapered soft tip at the distal end 204 of the device. If cooling is not being administered, and thus the lumen is not being used for aspiration, the lumen can serve as a standard central venous catheter lumen for delivering drugs or fluids to the central venous system. The aspiration lumen 216 may be reinforced to prevent collapse when aspiration is being applied. The suction lumen 216 may be used to draw blood from the vein distal to the balloon and carry the blood to the inlet of the temperature modulation system.

The device may contain a lumen, referred to as a proximal infusion lumen or cooling lumen, with one or more ports thereof located proximal to the balloon. The one or more ports may be cut or incised into a side of the cooling lumen of the multi-lumen tubing proximal to the balloon, and the cooling lumen may be sealed distal to the one or more ports. The cooling lumen may infuse a cooling fluid through a port located proximal to the balloon. This may serve the purpose of guiding a flow retrograde in a human blood vessel.

In some embodiments, one lumen may, for example, serve as a standard central venous catheter lumen for delivering drugs or fluids to the central venous system. For example, the outlet may be cut into a side of the catheter near the distal end 204 of the device, and the lumen may be sealed distally from the outlet.

One lumen may be an infusion lumen with its outlet located proximal to the balloon. It may infuse fluid through a port located proximal to the balloon. In some instances, it may be capable of communicating with more than one outlet port, one or more of which may be located proximal to the balloon and one or more of which may be located distal. This lumen may only communicate with the distal port 240 or only with the proximal outlet port at a time when the device is being used. The lumen may be capable of changing the port it communicates with based on input from a user. In the first orientation, the proximal port may be open and the distal port 240 may be closed upon inflation of the balloon. This may serve the purpose of guiding the flow retrograde in the human blood vessel. In a second orientation, which may occur upon deflation of the balloon, the proximal port may be closed and the distal port 240 may be open. This may allow the lumen to act as a standard central venous catheter lumen for delivering drugs or fluids to the central venous system. The two outlets may be cut into one side of the catheter, and the lumen may be sealed distal to the most distal outlet. Several methods of switching outlet lumens have been devised herein.

The device may contain a lumen, referred to as a distal infusion lumen or an flashback lumen, with one or more ports located distal to the balloon. One or more ports may be cut or incised into a side of the cooling lumen of the multi-lumen tubing proximal to the balloon, and the flashback and distal ports 240 of that lumen may be tapered soft tips at the distal end 204 of the device. The flashback lumen may infuse a normothermic or warmed fluid through one or more ports located distal to the balloon. This may serve the purpose of ensuring that the temperature of the heart and/or the temperature of the body does not drop below a desired level. The flashback lumen can receive a guidewire to facilitate placement of the device.

The device may have a multi-lumen conduit that may be located distal to the mounting feature, which is intended to enter the portion of the human body. The portion may be a customized multi-lumen (e.g., four-lumen) extrudate. The lower extrudate may require an antimicrobial coating that may be applied to the part to prevent entry into the body to prevent centerline-related bloodstream infections (CLABSI). The multi-lumen tubing may have (radiopaque) markings 207, which markings 207 allow the end user (who may be a healthcare professional placing the device) to determine how much of the lower tubing can be inserted into the patient. A taper, soft or tapered and soft tip may be added to the portion of the device. Radiopaque markers may be placed both at the distal tip 205 and only proximal to the proximal perfusion lumen. The sheath balloon may be thermally bonded to the conduit. The pipe may be reinforced with coiled reinforcement to provide the pipe with increased hoop strength and kink resistance. The coil may be made using stainless steel or nitinol. The sheath balloon may allow jugular vein occlusion when inflated such that fluid administered to a proximal infusion port located proximal to the balloon is directed retrograde toward the brain.

The proximal portion of the device may include one or more upper lumens with female luer-lock fluid connectors, cables and connectors for temperature sensors, and cables for additional temperature sensors or other sensors. These lumens may be marked to refer to their function, and labeling may be done using screen printing or pad printing. They may have different lengths and their luer connectors may have different colors so that they are easily distinguishable from each other.

The device may be placed in the internal jugular vein, between the medial and lateral heads of the sternocleidomastoid muscle, and outside the carotid artery. The device may be placed using the Seldinger technique under ultrasound guidance, where the device is inserted over a guidewire and doppler ultrasound may be used to ensure vessel occlusion upon balloon inflation. A system for fully or partially automating the insertion of the catheter may be used for the placement device.

Once the device is inserted, blood return from the insertion point may occur due to infusion through the proximal infusion lumen, which may result in local venous pressures of, for example, 30mmHg to 60mmHg or higher. To prevent fluid from leaking from the insertion point during use, the device may include a blood return prevention mechanism, such as a rubber grommet.

In some cases, the proximal multi-lumen tubing may be the illustrated tube profile. The outer diameter may be 2.5-10mm (7.5-30Fr), with some embodiments 6mm (18 Fr). The two lumens may have a fixed ratio of cross-sectional area surface area as these lumens will be used for aspiration and infusion. The total area of the aspiration lumen 216 may be 125% or more of the total area of the one or more infusion lumens, which may be used to reduce tremors and cavitation when attached to an extracorporeal circuit. In other embodiments, the outer diameter may be 1-5mm (3-15Fr), with a preferred embodiment being 3mm (9 Fr). In this case, one lumen may be 22 gauge (0.413 mm diameter) and one lumen may be 18 gauge (0.838 diameter). The multi-lumen tubing may be made of polyurethane (such as polyurethane).

The sheath balloon may have an inner diameter of 2.5-10mm (7.5-30Fr), with a preferred outer diameter of 6.1mm (18.3 Fr) and may be slightly larger (0-25% larger) than the tubing. The balloon may have the ability to expand to an outer diameter that is 200% (or more) greater than the uninflated outer diameter when inflated. In other embodiments, the sheath balloon may have an inner diameter of 1-5mm (3-15Fr), for example, where the outer diameter is 3.1mm (9.3 Fr). The balloon may be inflated to a target inflation diameter of 3-10ml of the fluid insert. The target expanded diameter may be 10-30mm or greater. The balloon may be made of polyurethane, such as thin extruded polyurethane. The balloon may be a compliant balloon. The balloon may have a thin wall that remains as flush as possible with the conduit.

The soft tip can be thermally bonded (reflowed) to the tube. One lumen may continue through the soft tip so that it exits outwardly from the distal tip 205 of the device so that it can be used to insert the device over a guidewire. The soft tip may be a different color than normal tubing so that it is distinguishable. The tip may be radiopaque.

The outlet ports on the device may be large enough so that they do not impede flow while the device is in use. The device may have pad printing or other indicia showing the length of the device inserted into the patient for a portion of the device (e.g., at least 6cm of the device). The length markings may be in 1cm increments.

1.2.1 pressure and temperature

In some embodiments, a catheter may be placed in the internal jugular vein, the expandable obturator expanded so that the vein may be occluded, and cryogenic fluid may be delivered retrograde through the catheter toward the brain and normothermic or hyperthermic fluid delivered anterograde through the catheter toward the heart. The pressure sensor or pressure sensing lumen of the device may be located in or near the internal jugular vein and may allow for measurement of the pressure in the internal jugular vein. The pressure sensor and/or other sensors or probes may send data to a data storage module to record or send to a control system of the extracorporeal system, which may change its flow rate or flow temperature or indicate based on the sensor data so that the user knows to manually change the settings. The data storage or control system may be part of the temperature modulation system described herein. In some embodiments, changes in flow rate or flow temperature may be made to ensure cooling of the brain as monitored by the tympanic probe or other replacement below or equal to a neuroprotective level of 32-33 ℃. The pressure sensor of the catheter may be used to monitor whether the brain or venous system is experiencing a pressure above that which may be considered safe. With these sensors or other data sources used as inputs, the system may be able to maintain hypothermia in the brain while maintaining the brain or venous pressure below an established safe threshold pressure, such as a pressure of 25 mmHg. The pressure threshold may be a time-weighted average of the pressure readings.

In another embodiment, one of the one or more temperature sensors of the device may be located at or near the atrial interface or at the suction port 238 of the device, and may allow for inferences of heart temperature to be measured by the surrogate. The temperature sensor and/or other sensors or probes may send data to a data storage module to be recorded, or to a control system of the extracorporeal system, or both, and interpretation of this data may cause the system to change its flow rate or temperature through the system based on the sensor data. It may also use this data to set alerts or reminders to get the user's attention and to remind them that the settings may need to be changed. This change in flow rate or flow temperature may be made, where possible, to ensure that the heart is maintained at a temperature warm enough to avoid arrhythmias, which may be above 32 ℃.

In other embodiments, the conduit means may use retrograde flow to provide selective cooling.

A pressure sensor or other means of measuring pressure may be integrated into the body of the catheter so that a measurement of fluid flow through the vasculature may be evaluated. One or more temperature sensors or other means of measuring temperature may be integrated into the body of the catheter so that the temperature of fluid flowing through the vasculature may be assessed. A control system may be implemented in which autologous blood may be pulled from the patient's venous system, modified through an extracorporeal circuit, and returned to the patient's venous system, possibly with a pump. Such modifications to the blood may include temperature modulation, oxygenation, or otherwise. The lumen of the catheter or the catheter itself may be insulated to avoid heat exchange.

1.3 additional features of infusion catheters

1.3.1 cage ball obturator (see FIG. 4)

Fig. 4 depicts an illustrative scenario for providing therapy with a catheter using a cage style ball obturator according to some embodiments of the present disclosure. In some embodiments, the ball obturator may be located at the following positions: wherein it can be non-occlusive to the lumen such that fluid delivery through the lumen can exit through the distal port 240. In another configuration, the ball obturator may be located in the following positions: wherein it may be occluded from the lumen such that fluid delivered through the lumen may exit through the proximal port. This may interrupt flow and may allow for the possibility of redirecting flow through the proximal port. The ball obturator can potentially be transferred according to user input using a pre-placed guidewire or other mechanism; such a transfer may allow the occluding ball to move so that it does not occlude a lumen potentially in a cage located at the exterior of the catheter. The cage may be composed of a flexible material so that the device may still have a flush outer surface; wherein the cage may not expand away from the surface of the device until desired by the user.

1.3.2 semi-cylindrical obturator (see FIG. 5)

Fig. 5 depicts an illustrative scenario for providing therapy with a catheter using a semi-cylindrical obturator, according to some embodiments of the present disclosure. The shunt can have a semi-cylindrical device referred to herein in the associated figures as an obturator. In one configuration, the obturator is oriented such that it occludes the perfusion port and the flow administered through the lumen is directed to the distal port 240. In another configuration, the obturator is rotated 180 ° and then the distal port 240 is occluded and the applied fluid is allowed to exit the irrigation port.

1.3.3 removable inner lumen (see FIG. 6)

Fig. 6 depicts an illustrative scenario for providing therapy with a catheter using a removable inner lumen, according to some embodiments of the present disclosure. In one embodiment, another catheter having a proximal port can be placed in the main catheter, where it can be non-occlusive to the lumen such that fluid delivery through the lumen can exit through the distal port 240. In another configuration, the catheter may be located at the following positions: wherein the proximal ports of the two catheters overlap or align such that fluid delivery through the lumen can exit through the proximal ports of the two catheters. The lumen may be translated or rotated according to user input. The internal lumen is removable and may be administered through any existing lumen of the main catheter body 202 to preferably direct fluid flow through the selected port(s). The inner lumen can have an opening that aligns with a selected port located on the main body of the main catheter, thereby blocking fluid flow through the port that does not have an aligned port located on the inner lumen.

1.3.4 curved tip for inferior vena cava Access

Fig. 7 depicts an illustrative scenario of providing therapy using a curved-tip catheter for inferior vena cava access, according to some embodiments of the present disclosure.

In some embodiments, the distal tip 205 of the device may have the ability to move between a compressed position and a released position as noted above. In the compressed position, the distal tip 205 may partially or completely bend upon itself to reduce the likelihood of injury to blood vessels in the body. In the relaxed position, the curved portion of the catheter tip may increase its distance from the unbent portion of the catheter tip. The catheter tip may be moved between the compressed and released positions using an elongate wire inside the catheter or by some other mechanism. The location of release of the catheter tip may assist the catheter tip in entering the inferior vena cava if the catheter tip extends into the right atrium.

1.3.5 non-occlusive balloon for mitigation of potential vessel collapse

Fig. 8 depicts an exemplary external view of a catheter with a non-occlusion balloon according to some embodiments of the present disclosure. Fig. 9 depicts an exemplary cross-section of a catheter with a non-expanding, non-occlusive balloon. Fig. 10 depicts an exemplary cross-section of a catheter with an expanded non-occlusive balloon according to some embodiments of the present disclosure.

A non-occlusive balloon may additionally be disposed on the infusion catheter near the aspiration port 238. The balloon may be inflated only during the removal of blood through the suction port 238, and inflation of the balloon will result in structural support to the vessel wall and relief of potential vessel collapse around the catheter body. The balloon should be placed on the catheter body and have a unique port for inflation. The balloon should be composed of multiple fluid channels connected to the inflation lumen through a single channel.

In its uninflated state, the balloon and accompanying channels will lie flush with the outer wall of the VCL.

Once inflated, all of the fluid channels will become filled with fluid until a maximum wall tension of the fluid channels and the outer wall of the balloon is reached. This will result in structural reinforcement of the vessel wall while mitigating vessel collapse that causes cavitation of the aspirated blood, while allowing blood to flow proximally through the aspiration port 238, if desired.

1.3.6 non-occlusive balloon for reducing risks

A similar non-occlusive balloon as previously described may alternatively be located distal to the lateral distal infusion outlet, such that it provides a protective "cushioning" effect for the tip of the catheter. In this way, the catheter tip minimizes interaction with surrounding tissue, thereby minimizing the risk of perforation or damage. This may be particularly significant in embodiments of such infusion catheters that are located distally in the right atrium of the heart. Such a balloon may help prevent the tip of the catheter from additionally passing through the tricuspid valve to the ventricle.

1.4 inflatable elements for suction (see FIG. 11)

Fig. 11 depicts an exemplary external view of a catheter having an expandable element to facilitate aspiration, according to some embodiments of the present disclosure. An expandable element, which may be an elastomeric balloon, may be disposed on the body of the catheter to help maintain an open flow path through the suction port 238 of the device. In its expanded configuration, the element may be of annular geometry such that it maintains the patency of the blood flow path drawn through the port on the catheter body, and may be particularly beneficial in situations where applied suction may occur. Otherwise the device is sucked up to the wall of the container in which it is located. The geometry may be such that it maintains the patency of the vessel and creates a distance between the body of the catheter and the vessel wall so that fluid drawn or delivered through the suction port 238 on the device has a usable flow path. The inflation lumen may communicate an inflation fluid between the main body of the catheter and the expandable member. The expandable member may further be tethered to the body of the catheter with a suture or equivalent tethering mechanism.

2.0 System for temperature modulation System

2.1 temperature modulation System (see FIGS. 12-15)

Fig. 12 illustrates a system suitable for incorporation into a catheter, in accordance with some embodiments of the present disclosure. In some embodiments, a system may provide for moving a fluid through a fluid circuit and adjusting a characteristic of the fluid. The system may be referred to as a therapy delivery system. Fluid movement may be generated by one or more pumps or pumping mechanisms. The temperature characteristics of the fluid may be adjusted by one or more heat exchangers or similar temperature adjusting devices. The oxygenation characteristics of the fluid may be adjusted by one or more oxygenators. In some cases, the controller may be used to adjust various aspects of the therapy delivery system. The console may be used to interface or interact with and monitor the therapy delivery system. The therapy delivery system can be connected to an infusion catheter as described herein to deliver selective therapy to an organ or group of organs. If the therapy delivery system meets parameters that may be detrimental to the patient, such as excessive cooling, then countermeasures for selective therapy may be implemented and controlled by the control system and monitored on the console.

In some embodiments, fluid movement may be generated by one or more pumps or pumping mechanisms, thereby creating one or more fluid circuits of the therapy delivery system. A pump or pumping mechanism may be used to create suction at one or more inlets of the fluid circuit and to expel fluid at one or more outlets of the fluid circuit. The pump or pumping mechanism may flow in a first direction and a second direction, and the flow direction may be switched at a specific time. The direction and rate of flow in the loop may vary over time. The pump may be a centrifugal pump or a peristaltic pump. When the fluid being moved is blood or the like, a centrifugal pump may be used to minimise the risk of hemolysis. For centrifugal pumps that come into contact with blood or other bodily fluids, the pump head may be replaced and discarded after a single use or after only a few uses. The disposable pump head may be manipulated by using a non-contact force application method such as magnetic actuation. The pump may drive flow through the system at a flow rate of, for example, between 0ml/min and 2L/min. The pump circuit may contain safety mechanisms, such as pressure relief valves, check valves, etc., to ensure that the circuit continues to operate under safe operating conditions, such as to maintain the pressure in the circuit below a specified safety threshold. The flow rate or pressure provided by the pump may be regulated by a control system, as described herein. In some cases, the pumping mechanism may be controlled by an operator. In some scenarios where pumping is operator controlled, pumping may be performed using a fluidic mechanical force input from the operator. Such mechanically driven pumps may be used when the system is malfunctioning or there is no electrical energy input required for operation.

In some embodiments, the fluid circuit may be coated with heparin or other similar anti-coagulation medium to prevent blood coagulation in the pump and fluid circuit. Some or all of the fluid paths of the fluid circuit may be insulated to minimize thermal communication of the pump and the fluid in the fluid circuit with the ambient environment. Some or all of the fluid paths of the fluid circuit may be partially or completely in contact with an ice pack or gel ice pack, which may be composed of a mixture of water and possibly one or more other fluids (e.g., propylene glycol) to help maintain the fluid in the cooling circuit at a desired temperature.

The temperature of the fluid may be modulated by one or more heat exchangers or similar temperature modulating devices. The temperature modulating device may heat or cool the fluid passing through the fluid circuit. In some embodiments, one or more auxiliary fluid circuits may be in thermal communication with one or more therapy delivery system fluid circuits. In this embodiment, the point of heat exchange between the one or more auxiliary fluid temperature modulation circuits and the fluid circuit of the therapy delivery system may be a sterile heat exchange unit. The sterile heat exchange unit may be disposable and discarded after contact with the fluid of the fluid circuit. The auxiliary heat exchange loop may be in thermal communication with one or more of the therapy delivery system fluid loops using thin metal plates, and the design of the therapy delivery system may use a parallel flow or counter flow heat exchange mechanism, a shell and tube heat exchange mechanism, a fin or finless tube heat exchange mechanism, a U-tube heat exchange mechanism, a plate and frame heat exchange mechanism, another similar heat exchange mechanism, or some combination thereof. The secondary fluid heat exchange loop may circulate water, a refrigerant fluid, or some other fluid having properties optimized for heat transfer. The auxiliary fluid temperature modulation circuit may include a compressor to drive fluid flow, operate the refrigeration circuit, and remove heat. The circuit may also include a condenser and an evaporator in thermal communication with the system surroundings. An expansion valve may be used to remove pressure from the fluid at one or more points in the fluid circuit. The one or more secondary fluid temperature modulation circuits may include one or more peltier devices to regulate the temperature of the fluid in the second fluid circuit. One or more auxiliary fluid temperature modulation loops may use an ice bath as a source of cold fluid for circulation through the heat exchanger. The auxiliary fluid temperature modulation circuit may use fans, heat sinks, or other methods of increasing the transfer of thermal energy to dissipate heat from the temperature modulation device, particularly in the condenser and evaporator. Some or all of the fluid paths of the temperature modulating device may be insulated to minimize thermal communication of the fluid in the system with the ambient environment. The auxiliary fluid temperature modulation circuit may also contain heating coils or other similar heating sources to heat fluid passing through the heat exchanger, thereby heating all or a portion of the fluid passing through the fluid circuit of the one or more therapy delivery systems. An auxiliary fluid circuit may be used to cool all or part of the blood passing through the fluid circuit of the therapy delivery system, and the cooled blood may be infused through the cooling lumen of the infusion catheter. An auxiliary fluid circuit may be used to heat or maintain the temperature of some or all of the blood passing through the fluid circuit of the therapy delivery system, and the warm blood may be infused through the anti-warm lumen of the infusion catheter. A fluid flow adjustment mechanism (e.g., one or more valves) may be used to indicate how much flow from the fluid circuit (if any) of the therapy delivery system is being heated or cooled by the auxiliary circuit. For example, one or more valves or other fluid distribution systems may direct 20% of the flow entering from the suction inlet to be cooled by the cooling auxiliary circuit, while the other 80% of the flow is directed to pass through the heating auxiliary device heating circuit. There may be two or more flow branches and any number of combinations and conditions may be applied to these different flow paths.

The oxygenation characteristics of the fluid may be adjusted by one or more oxygenators. The fluid in the fluid circuit may pass through the oxygenator and be filled with oxygen. The oxygenator may have a sterile, disposable oxygenation unit that may be discarded after contact with the fluid in the fluid circuit.

Fig. 13 illustrates a system using a controller adapted to be incorporated into a catheter, according to some embodiments of the present disclosure. Fig. 14 illustrates a system using an oxygenator and a controller suitable for incorporation into a catheter, according to some embodiments of the present disclosure. In some embodiments, the controller may be used to adjust various aspects of the therapy delivery system. The controller may modulate the pressure of the fluid in the fluid circuit, the temperature of the fluid, the flow rate of the fluid, the oxygenation of the fluid, similar system characteristics, or some combination thereof. The pump, heat exchanger, oxygenator (if present), and other system components, such as temperature, pressure, and flow rate sensors, may be in communication with the controller, and each connection may be made using one or more communication cables. When modulating the temperature of the fluid, the controller may modify aspects of one or more auxiliary fluid heat exchange circuits, such as flow rate, temperature, or pressure in the second fluid circuit, which may be in thermal communication with the therapy delivery system. The controller may take inputs from sensors, such as temperature, pressure, flow rate sensors, etc., and use these inputs to modify the therapy delivery system. The temperature measurements may be collected using tympanic membrane, nasopharynx, duct-embedded or catheter-based sensors, or some combination thereof. The pressure input may be collected via a conduit device and/or from a sensor in an associated tube with which the system may be in fluid communication. The controller may be a PID (proportional integral derivative) controller, a Programmable Logic Controller (PLC), another control system, or the like. Algorithms may be used to control the characteristics of the cooling system based on the previously described sensor inputs. The algorithm can monitor the temperature of the target site, e.g., the temperature of one or more target organs or regions proximate to or at a similar temperature to the one or more target organs, and adjust the therapy delivery system to modify the temperature of the target site. The target organ for selective cooling may be the brain, which may be targeted by the presence of stroke, to potentially provide neuroprotection and reduce brain damage. The temperature of the heart may also be strategically placed, either directly or indirectly, using temperature sensors within the body, outside the body, in the therapy delivery system (e.g., associated conduits), or in other ways to ensure that it does not drop to monitor temperatures below a known risk, temperatures near 33 ℃ increasing the likelihood of arrhythmia. In some embodiments, indirect measurements of heart temperature may be inferred by a temperature sensor placed on a catheter, which may be located on or in the catheter body at or near the ostium junction. An emergency cutoff temperature may be set so that if the temperature measured by a particular temperature probe is too low, e.g., 32 degrees C near or at the heart, the system will slow the flow rate of fluid through the fluid system or shut down completely. An algorithm may combine the known volume and temperature of the hot and cold perfusate, the known volume and temperature of the inspired blood, and the temperature read from the device thermistor, possibly together with patient parameters such as weight, heart rate, blood pressure, body temperature (rectal or bladder probe) to infer the expected heart temperature. This can be done by solving various known temperatures and volumes delivered and aspirated to the heart and calculating the resulting mixed temperature blood that the heart will experience.

The emergency shutdown measurement may come from a temperature sensor that measures the temperature at or near the heart or in the fluid path of the therapy delivery system, and slowing or stopping the flow in response to the temperature being too low may allow the system to prevent the heart from reaching a dangerous temperature that may be below 32 ℃. The flow rate of warmed or normothermic blood through the flashback chamber may also be used to prevent the heart from reaching dangerous temperatures. Similarly, the control system may take input of a target temperature of the target organ to adjust the flow rate or other parameters of the therapy delivery system. In some embodiments, the target brain temperature as measured by the nasopharyngeal or tympanic temperature probes can be greater than or equal to 33 ℃, and the control system can increase the flow rate of the cooling fluid, decrease the temperature of the cooling fluid being used, or decrease the flow rate of the warm or normothermic inverse warm fluid to reach and maintain this target brain temperature. The temperature of the heart may be monitored directly (e.g. with a temperature probe in the right atrium) or indirectly to ensure that cooling of the brain does not cause the heart to dangerously low temperatures, e.g. temperatures below 32 ℃.

In some embodiments, the algorithm may adjust a characteristic of the fluid system in response to a recanalization condition of the occluded blood vessel. For example, in stroke patients undergoing thrombectomy, the cooling and flow rate of the system may be increased to lower the temperature of the brain, thereby allowing neuroprotective hypothermia to reduce the risk of reperfusion injury. The temperature of the brain and the temperature difference between the brain and the body can be adjusted according to the medical condition of the patient or the time after they have received some other treatment (e.g., thrombectomy). The control system may be based on parameters of the medical imaging modulation system. For example, a CT scan or MRI of a stroke patient may indicate that the patient has a large amount of brain tissue that can be preserved, in which case the controller may increase the flow rate of cooling, decrease the temperature of the fluid, increase the oxygenation of the fluid, or otherwise adjust the system to better save the tissue at risk.

In some embodiments, the temperature measured using a nasopharyngeal or tympanic temperature probe near the brain can be used to increase the flow rate of the pump or decrease the temperature of the fluid in the therapy delivery system to decrease the temperature of the brain according to the control system algorithm. The control system may also adjust the temperature and flow rate of the heating fluid delivered to the flashback port of the infusion catheter to increase or maintain the temperature of the heart. The control system can control the flow rate and temperature of the fluid to achieve a specified target temperature in the brain and heart. If the temperature measurement at or near the target organ (e.g., heart) is too low, as measured by a device placed in the patient's central venous system, it may be desirable to heat the target organ; the controller may reduce the flow rate of the pump, increase the temperature of the fluid, or change the path to or from the heart as dictated by the control algorithm. The pressure generated by the output of the therapy delivery system may be monitored by a sensor on the infusion device, possibly a pressure sensor or pressure lumen 217 placed near the infusion port of the device. The system may reduce the flow rate or pressure of the therapy delivery system to prevent over-pressurization near the outlet of the therapy delivery system. In this example, the output infusion of the therapy delivery system may be in a human blood vessel, such as a vein, and the measured pressure may be the pressure generated by the infusion into the vein to assess whether the pressure or flow rate of the infusion requires a reduction in the therapy delivery system to reduce safety risks, such as edema where the target organ is the brain.

The console may be used to interface or interact with and monitor the therapy delivery system. The console may be designed for ease of use by the operator. The console may have a screen, such as a touch screen or display screen, that allows the user to adjust the characteristics of the system based on the information displayed on the screen. Alternatively, dials, buttons, and other mechanical control mechanisms may be used to modify the characteristics of the fluid system. Temperature, pressure, flow rate and similar sensors may be operatively connected to the cooling console through the controller and may report measurements on a screen. The console may be able to collect and store data over a period of time and report the values of the sensor readings over a period of time. A physician or other medical professional may use the console to monitor the heart temperature, brain temperature, or both, of a patient suffering from stroke being treated with the therapy delivery system. When the situation reaches a dangerous level, the console may alert the care provider and prompt a change in the therapy delivery system parameters.

Fig. 15 illustrates a system using a controller incorporating a catheter according to some embodiments of the present disclosure. In some cases, the therapy delivery device may be fluidly connected to the previously described infusion catheter at one or more points. One or more inlet ports of the therapy delivery system may draw from the draw port 238 of the infusion catheter, and one or more outlet ports of the therapy delivery system may infuse fluid conditions that may have been adjusted in temperature, oxygenation, or both through the infusion port of the infusion catheter. One of the infusion lumens, e.g., the infusion lumen proximal to the expandable occlusion element outlet, may be connected to the outlet of a therapy delivery device that delivers cooled fluid to the proximal infusion lumen, while the other of the infusion lumens, e.g., the infusion lumen at the expandable occlusion element distal outlet, may be connected to the outlet of a therapy delivery device that delivers warmed or body temperature fluid to the distal infusion outlet. One or more sensors of the infusion catheter may communicate with the controller or another component of the therapy delivery system to transmit measurements from one or more sensors in the device. The therapy delivery system may control the temperature, flow rate, pressure, and oxygenation infused through the infusion catheter. In embodiments where cooling may be delivered to the brain of a stroke patient, the cooling may increase vasodilation of arteries in the brain and thus improve collateral circulation to portions of the brain isolated from blood flow.

Fig. 16 illustrates a system using a controller incorporating a catheter for use with a patient, according to some embodiments of the present disclosure. In embodiments of a combined infusion catheter and therapy delivery system, the infusion catheter may be placed in the central venous system of a patient, such as the internal jugular vein (or femoral vein), and may be used to selectively cool an organ, such as the brain. The system may be used to cool, oxygenate, or otherwise provide therapy to the brain of a stroke patient to potentially reduce ischemic injury.

The inflatable occluder may be inflated to occlude a vein in which an infusion catheter may be placed. In some embodiments, the inflatable obturator, which may be a balloon, may be inflated with a cold fluid, such as saline, to enhance cooling. The suction port 238 of the therapy delivery system may be used to draw blood through the suction lumen 216 of the infusion catheter, flow the blood through the fluid circuit of the therapy delivery system, and perform infusion of the catheter through the one or more infusion ports of the infusion set. Since the vein in which the infusion catheter may reside is occluded by the expandable obturator of the catheter, some of the infusion fluid from the therapy delivery system, i.e., fluid infused proximal to the expandable occlusion element, may be retrograde guided in the vessel. Some other portion of the fluid infused through the infusion catheter, i.e., the portion infused distal to the inflatable occlusion element, may be directed anterogradely in the blood vessel to the heart. This may enable selective brain therapy, where oxygen may be delivered, the brain may be cooled, a drug may be delivered, some other therapeutic agent may be delivered, or some combination thereof. The brain may be cooled to a cryogenic level of 23-28 ℃, which may significantly slow metabolism, thereby providing neuroprotection during cardiac surgery. Alternatively, the brain can be cooled to 33 ℃ or less, which animal studies indicate has neuroprotective effects. When the brain is cooled to 33 ℃ or less, it may be advantageous to complete the brain cooling quickly in a time of 0-30 minutes after the cooling is started, in order to reduce the risk of reperfusion injury.

The pressure of retrograde perfusion can be monitored to ensure that it does not exceed a level known to be safe in the brain, such as continuous intracranial pressure (ICP) of greater than 25 mmHg. To mitigate the potential for dangerously high levels of ICP, the inflatable obturator may be periodically uninflated to relieve pressure in the fluid system in which the device may reside. The cooling system may also control fluid flow into and out of the expandable obturator port of the infusion device. The cooling system can circulate a cooling fluid in the inflatable obturator of the device to increase the amount of cooling delivered to the selected organ. The connection point between the therapy delivery system and the infusion catheter may be a luer connector.

The combination system, infusion catheter and therapy delivery system may be adapted to deliver selective cooling therapy during patient transfer (e.g., in an ambulance). To accomplish such treatment, the therapy delivery system may need to be enclosed in a container having a volume of between 1-5 cubic feet, which may be small enough to fit in an ambulance. The therapy delivery system may be operated from power supplied by an ambulance or a battery. The infusion catheter may have features such as ultrasound guidance that enable the user to ensure that the device can be properly placed, which makes it safely insertable by an EMT, nurse, or other medical professional on an ambulance. Ultrasound guidance may include the use of doppler ultrasound to assess whether the balloon is occluding the vessel, and may utilize inflation of the balloon with an agitated solution to help visually confirm that an expandable obturator, which may be a balloon, may have expanded. The infusion catheter may be attached to the patient at one or more attachment points to ensure that the infusion catheter remains in the correct placement position during shocks and vibrations experienced during ambulance travel.

Countermeasures for selective treatment may be implemented if the therapy delivery system may be at risk of causing injury. For example, if the therapy delivery system is used to selectively cool the brain, the heart may be cooled from a cooling fluid that passes through the brain and reaches the heart. To prevent the heart from cooling too deeply, a heating strategy may be used. In some embodiments, warmed fluid may be delivered through the lumen of the infusion catheter, typically near the heart, to heat the tissue of the heart. In some embodiments, a warmed or body temperature fluid may be infused through the anti-warming lumen of the infusion catheter to heat or maintain the temperature of the heart. Such heated or body temperature fluid may be delivered to the distal end of the inflatable obturator of the device, in the internal jugular vein, the brachiocephalic vein, the superior vena cava, the right atrium of the heart, or the inferior vena cava. A heating blanket, forced air heating system, heating pad or the like may be used to transfer heat from the outside through the patient's skin. These countermeasures for selective treatment can be controlled by the control system, so that more countermeasures can be implemented when the sensors are likely to measure in a range considered dangerous. For example, a temperature sensor in or near the heart may alert the control system that the heart may reach a dangerous level, and thus the control system may increase the counter warming.

In another embodiment of a combined system, an infusion catheter may be placed in the arterial system of a patient, such as the carotid or femoral artery, and may be used to selectively cool an organ, such as the brain or limb.

In at least one embodiment, the disposable components of the therapy delivery system can be entered into a prepackaged kit. The kit and components therein may be sterilized. The kit may include one or more disposable pump heads, one or more disposable heat exchangers, one or more oxygenation assemblies, one or more temperature sensors, one or more pressure sensing devices to measure pressure conduits from an open lumen, disposable tubing lengths having one or more diameters, or some combination thereof. The heat exchanger and oxygenator, if present, may be a combined component that may function as both a heat exchanger and an oxygenator.

2.2 Selective Cooling of the heart against temperature (see FIGS. 17A-17B)

Fig. 17A illustrates a system using selective cooling and cardiac flashback, according to some embodiments of the present disclosure. The system may include a controllable pump or other means of generating a pressure head, a heat exchanger or other cooling medium device, a temperature sensor or other device for measuring body temperature, and a catheter or other type of venous access device, herein labeled as a "catheter", that may direct fluid to a preferential direction, such as to the patient's heart during a stroke or cardiac arrest. A temperature sensor near the heart can be used to monitor whether the heart is likely to reach dangerously low temperatures, for example, temperatures at or below 32 ℃, which are known to cause arrhythmias and ultimately cardiac arrest. The system may draw blood or other fluids from one or more ports of the catheter; the fluid may be withdrawn from the original fluid system, such as the body, may be temperature modulated by a heat exchanger, and may be infused back into the original fluid system at a different temperature. Fluid infused into the original fluid system, which may be the body, may be directed to a structure to be selectively heated, such as the heart. The flow rate or another parameter of the pump system, which may be controlled by a user, a control system, or other means, may be adjusted in response to an input to the control system, such as an input from a temperature sensor. Sensors such as nasopharynx, tympanic or other temperature sensors may be used as inputs to control parameters of the system, such as the flow rate of the pump or the cooling rate of the heat exchanger. Additional sensors, such as temperature sensors measuring heart temperature, may be used to determine whether the flow rate or heat exchange rate should be adjusted. The system may monitor the patient's brain and heart temperature directly or indirectly and the system may make suggestions to the user on how to adjust the system to maintain the desired temperature, e.g. maintain a warm temperature in the heart to prevent arrhythmias, a temperature above 32 ℃. The system may contain a user interface to allow control of the system and monitoring of important parameters such as flow rate, temperature and pressure of the perfusate. The catheter may contain additional lumens for delivering drugs or other agents, pressure sensing, or other functions.

In practice, the system may have a heat exchanger that ensures that the blood is maintained at 32 ℃ and that the blood can be heated to or above this temperature. This may be autologous blood and may be collected by the same catheter that delivers the temperature regulated blood back to the patient. The pump may adjust its flow rate in the range of 0-2000ml/min, for example, based on one or more temperature sensors or other sensors disposed in or on the catheter body at or near the luminal interface, which may be used as a proxy for heart temperature or another organ temperature. Temperature sensors in or on the infusion catheter may also be used to de-vasculature temperatures at other points. In addition, the blood may be passed through an oxygenator in addition to or in place of the heat exchanger.

The system is coupled to a catheter, and may be capable of drawing, temperature regulating, and re-infusing autologous blood to one or more target areas of the body at one or more target temperatures or oxygenations.

Fig. 17B illustrates a system for using inverse temperature selective cooling of a heart with a catheter in a patient according to some embodiments of the present disclosure. In some embodiments, the catheter may be placed in the internal jugular vein. One example may include extracorporeally cooling a portion of blood drawn through the suction port 238 of the catheter and re-infusing the portion of blood through a port near the occlusion body on the catheter, cooling and possibly oxygenating, such that targeted brain cooling may be achieved. At the same time, a portion of the blood that may be drawn through the device (or maintained at body temperature) is heated (or re-infused) through a port remote from the inflatable obturator, so that the heated blood can be preferentially directed to the heart. Thus, for example, inflatable obturator proximal cooling and inflatable obturator distal warming may be achieved for targeted brain cooling while maintaining near normothermia in the heart. The pump may adjust its flow rate in the potential range of 0-2000ml/min, for example, based on the distal tip 205 (as representative of heart temperature) from the tympanic temperature and catheter temperature sensors as representative of brain temperature. Using these sensors or other data sources as inputs, the system may be able to warm the heart enough to avoid arrhythmias, e.g. above 32 ℃.

2.3 control System

Fig. 18A is a block diagram of an illustrative system using a controller adapted to be incorporated into a catheter, in accordance with some embodiments of the present disclosure. Fig. 18A shows a schematic view of an illustrative device of a system 900, the system 900 including a catheter 902, a cooling heat exchange assembly 904, a heating heat exchange assembly 905, a controller 910, a console 918, and several exemplary sensors, including a brain temperature sensor 922, a heart temperature sensor 924, a pressure sensor 926, a flow rate sensor 928, and other sensors 929. These components may be installed on the local computing system, or may be remote components (e.g., remote servers, clouds, mobile devices, connected devices, etc.) that are wired or wirelessly connected to the local computing system. Generally in system 900, controller 910 controls the temperature and pump flow rate of each of cooling heat exchange assembly 904 and heating heat exchange assembly 905 based on input received from

sensors

922 and 929 and instructions to, for example, maintain safe patient treatment.

The control circuit 911 may be based on any suitable processing circuit, such as the processing circuit 912. As referred to herein, processing circuitry is understood to refer to circuitry based on one or more microprocessors, microcontrollers, digital signal processors, programmable logic devices, Field Programmable Gate Arrays (FPGAs), Application Specific Integrated Circuits (ASICs), and the like, and may include multi-core processors (e.g., dual, quad, hexa, eight, or any suitable number of cores). In some embodiments, the processing circuitry is distributed across multiple separate processors or processing units, such as multiple processing units of the same type (e.g., two INTELCOREi7 processors) or multiple different processors (e.g., one INTELCOREi5 processor and one Intel Kurui i7 processor). Some embodiments may use multiple controllers, each controlling, for example, at least one corresponding heat exchange assembly or other system component. In some embodiments, the control circuit 911 executes instructions stored in a memory (e.g., memory 914). For example, the instructions may cause the control circuit 911 to control the performance of the fluid heating and cooling operations described above and below.

The memory/storage 914 may be an electronic storage that is part of the control circuit 911. As referred to herein, the phrase "electronic storage" or "storage" should be understood to mean any means, computer software, instructions and/or firmware, such as random access memory, hard disk drive, optical drive, solid state device, quantum storage device, or any other suitable fixed or removable storage device, and/or any combination thereof, for storing electronic data. Non-volatile memory may also be used. The circuitry described herein may execute instructions comprised in software that runs on one or more general-purpose or special-purpose processors.

The controller 910 may receive and transmit data via an input/output (I/O) path 916. The I/O path 916 is communicatively connected to control circuitry 911, the control circuitry 911 including processing circuitry 912 and storage (or memory) 914. The control circuit 911 may send and receive commands, requests, and other suitable data using the I/O path 916.

In some embodiments, the controller 910 may receive sensor data from (and/or send requests to) e.g., brain temperature sensor 922, heart temperature sensor 924, pressure sensor 926, flow rate sensor 928, and other sensors 929 using the I/O path 916. In some embodiments, connections between components may be facilitated by one or more buses, such as a Peripheral Component Interconnect (PCI) bus, a PCI-Express bus, or a Universal Serial Bus (USB). Using such a bus, a computing environment may be able to integrate many components, many PCBs, many remote computing systems. One or more system management controllers, such as control circuit 911, may provide data transfer management functions between the bus and their integrated components. Such a management controller may facilitate the orchestration of the arrangement of these components, which may each execute an application with separate instructions within a defined time frame.

In some embodiments, the I/O path 916 may function in conjunction with the network interface 920. Network interface 920 may include an ethernet connection or a component network (LAN), Wide Area Network (WAN), intranet, or the internet forming a wireless 802.11b, g, a, or n connection to local. In some embodiments, controller 910 may communicate with console 918 through a network interface 920. The I/O path 916 can connect the control circuit 911 (and in particular the processing circuit 912) to one or more network interfaces 920, which network interfaces 920 in turn connect the controller 910 to other devices on a network (e.g., sensors 922. 929, heat exchange components 904. 905, console 918, etc.). Controller 910 may be connected to console 918 via an I/O path 916 and/or a network interface 920. The console 918 may include, for example, a monitor, a dial, and/or an input device such as a mouse, a keyboard touch screen, etc. to facilitate creating, modifying, or accessing instructions for the controller 910 and the system 900.

In system 900, controller 910 is communicatively coupled to cooling heat exchange assembly 904 and/or heating heat exchange assembly 905. Controller 910 may communicate instructions to each of cooling heat exchange assembly 904 and/or heating heat exchange assembly 905, for example, as set temperatures and/or flow rates for each heat exchange assembly.

In some embodiments, a cooling heat exchange assembly 904 may be used to provide cooling fluid to the catheter 202 to allow the cooling fluid to flow to the brain. The heat exchange assembly 904 includes a pump 906 and a heat exchanger 908. In some embodiments, heat exchange assembly 904 may be incorporated into a heat exchange loop. In some embodiments, heat exchange assembly 904 may include one or more flow rate sensors, such as flow rate sensor 928, to measure the outlet flow rate.

In some embodiments, an warming heat exchange assembly 905 can be used to provide a normothermic or warming fluid to the catheter 202 to allow the warming fluid to flow to the heart. Heat exchange assembly 905 includes a pump 907 and a heat exchanger 909. In some embodiments, heat exchange assembly 905 may be incorporated into a heat exchange loop. In some embodiments, heat exchange assembly 905 may include one or more flow rate sensors, such as flow rate sensor 928, to measure the outlet flow rate. Some embodiments may not use back heating from heating heat exchange assembly 905.

The system 900 may use a number of sensors to collect body and/or fluid temperatures. For example, brain temperature sensor 922 may include one or more thermistors placed within the patient. In some embodiments, brain temperature sensor 922 may be one or more of a nasopharyngeal temperature probe, a tympanic temperature probe, or an intraparenchymal temperature probe. In some embodiments, an intracranial pressure (ICP) probe including a temperature sensor may be used. Other thermistors or temperature sensors on or near brain tissue may be used to approximate the actual brain temperature. For example, the brain temperature may be estimated and/or measured by the agent. In some embodiments, for treatment, the brain temperature should be between 0 and 36 ℃. In some cases, the brain temperature may be estimated, for example, using a probe that is not near the brain. For example, based on received sensor measurements, it may be inferred that the brain temperature is a few degrees higher than the received brain temperature measurements.

Cardiac temperature sensor 924 may include one or more thermistors, such as thermistors in or on a catheter inserted in the patient. For example, when the distal end 204 of the catheter is inserted into the vena cava or right atrium of a patient, the catheter 902 can be an intravenous infusion catheter as described herein. In some embodiments, the cardiac temperature sensor 924 can be placed distal to the occlusion element. Some catheter embodiments may include a cardiac temperature sensor 924 located distal to the one or more suction ports 238. Positioning the heart temperature sensor 924 on or near the distal tip 205 of the catheter will allow the distal tip 204 to be at or near the atrial junction and/or the right atrium. Placement of a thermistor at the atrial boundary and/or near the right atrium can provide an approximate measurement of heart temperature. In some embodiments, placement of the thermistor in the superior vena cava, e.g., not at the caval junction, may also be suitable for use in approximating cardiac temperature. In some embodiments, a temperature sensor may be placed in the aspiration tube, for example, a tube that carries blood from the catheter to one or more heat exchange assemblies.

Calculating an approximate heart temperature may be more accurate than an approximate brain temperature because cooling the brain has a wider temperature range than a safe heart temperature. In particular, it is considered safe to keep the heart temperature above 32 degrees celsius, while efforts to keep the heart temperature at 36-37 degrees celsius are optimal. If the calculated heart temperature falls below 32 ℃, the pump 906 of the cooling heating assembly 904 may be adjusted to reduce or eliminate cold flow, while the pump 907 of the heating assembly 905 may continue or may increase. In some embodiments, the cooling system may be shut down if the calculated heart temperature falls below 32 ℃.

The measured and approximated heart temperature may be calculated in several ways. Some embodiments may use a thermistor on the catheter as a proxy for the heart temperature, where the temperature may be estimated. For example, if the temperature sensor reading in the vena cava is greater than 34 ℃, then the heart temperature can be assumed to be at least 35 ℃. Some embodiments may use a thermistor in the aspiration lumen 216 as a proxy for heart temperature. Some embodiments may use a thermistor on the device and a thermistor in the aspiration lumen 216, where redundancy increases safety.

Some embodiments may use the measured return volume and the temperature of the patient's superior and inferior vena cava to calculate an approximate heart temperature. For example, based on these inputs, controller 910 may determine the volume and temperature of the mixture of fluids returning to the heart. For example, the SVC fluid volume can be calculated from the known volume and temperature of the cold fluid delivered to the brain and the warm fluid delivered to the heart, and the temperature of the SVC or the temperature of the suction device measured by a thermistor on the device. Lumen 216. the IVC fluid volume can be determined using an approximation based on the calculated SVC volume, i.e. SVC is about 35% of cardiac output and IVC is 65% of cardiac output. Based on this ratio, the IVC volume is approximately equal to the product of 65 times the SVC volume divided by 35. If the SVC has a flow rate of 350ml/min, the IVC flow rate can be assumed to be 650ml/min. The heart temperature can be inferred by a combination of the assumed volume and the temperature returned by the combination of SVC and IVC. Generally, if the SVC regurgitation is above the safe threshold temperature of the heart, it can be assumed that the heart is at or above this temperature, because the IVC flow rate will typically only heat the heart in addition, rather than cool the heart.

In some embodiments, the other sensors 929 may include other temperature sensors, for example, to measure temperature for safety and redundancy. In some embodiments, the body temperature may be measured by a rectal temperature probe, a bladder temperature probe, and/or an esophageal temperature probe. Body temperature may be important for some calculations of heart temperature. In some embodiments, the tubing temperature (e.g., a thermistor in the catheter lumen or tubing of the heat exchange circuit) may be used to verify whether the controller 910 is delivering the desired temperature to the body for cooling or heating. In some embodiments, other sensors 929 may measure flow rates in the tubing and/or lumen, for example, flow rates through the aspiration lumen 216. The pressure sensor 926 and/or other sensors 929 may include, for example, a standard patient monitor connected to the open pressure lumen 217 of the conduit.

Fig. 18B depicts an illustrative flow diagram of a process for regulating a therapy system using a controller and incorporating at least one heat exchange assembly, in accordance with some embodiments of the present disclosure. In this case, the heat exchange assembly is controlled to cool the fluid flowing to the brain while maintaining a safe heart temperature. Process 930 includes steps for analyzing the sensor data to determine how to adjust the flow rate and temperature of the heat exchange assembly. Some embodiments may utilize a control engine stored and executed by one or more processors and memories of a controller, such as the controller 910 or other device that performs the steps of the process 930 depicted in the flowchart of fig. 18B. Some embodiments may use process 930 to initially set the temperature and flow rate of the brain cooling therapy system. Some embodiments may use process 930 to maintain and adjust the temperature and flow rate of the brain cooling therapy system.

At step 932, the temperature near the brain is measured. For example, the brain temperature may be measured by the brain temperature sensor 922 of fig. 18A. As shown in fig. 18A, it may include one or more thermistors disposed within the patient. For example, brain temperature may be estimated and/or measured by a proxy, for example, using nasopharynx and/or tympanic temperature probes.

At step 934, the temperature in the vicinity of the heart is measured. The heart temperature can be measured/calculated in a number of ways. For example, the cardiac temperature sensor 924 of fig. 18A may be used. Cardiac temperature sensor 924 may include one or more thermistors, such as thermistors in or on a catheter inserted into the patient, such that the thermistor is located on or near distal tip 205 to allow distal end 204 to be located at or near an atrial boundary and/or the right atrium of the heart. In some embodiments, the heart temperature may be inferred based on the temperature and volume measured for the superior vena cava (or SVC and IVC combination), as discussed above.

At step 936, the flow rate is measured. In some embodiments, the flow rate may be set and/or measured by a pump that is part of a heat exchange assembly, for example, to cool fluid flowing to the brain or heat fluid flowing to the heart. In some embodiments, separate sensors may be used to determine the flow rates in the various veins or arteries.

At step 940, the controller receives measurements of brain temperature, heart temperature, and flow rate. In some embodiments, a controller, such as controller 910 of fig. 18A, may receive sensor measurements via I/O path 916 and/or network interface 920.

In step 942, control determines whether the heart temperature is normal. In some embodiments, the heart temperature may be calculated by the controller or by another processor prior to transmission to the controller, if not directly measured. For safety reasons it is important that the heart temperature is around 36-37 ℃. In some cases, if the heart temperature drops below a certain temperature, for example 32 ℃, for example if the occlusion element of the catheter accidentally contracts, all cooling should be stopped immediately and closed urgently.

At step 944, if the controller determines at step 942 that the heart temperature is not ambient, then the flow rate of the cooling heat exchange assembly is adjusted by the controller. For example, if the heart temperature becomes too low, the controller may decrease the flow rate of the cooling heat exchange assembly, thereby producing cold fluid to the brain. In some embodiments, the flow rate may be adjusted based on a ratio of the received body temperature and the flow rate of the cold fluid at the set temperature flowing to the cerebral vasculature. In some embodiments, the temperature may be adjusted. In some embodiments, the controller sends commands to the heat exchange assembly to adjust the flow rate of the pump. For example, the controller 910 of fig. 18A may send instructions to the cooling heat exchange assembly 904 via the I/O path 916 and/or the network interface 920 to set the flow rate of the pump 906 and/or adjust the temperature of the heat exchanger 908. In some cases, although not very common, when cooling only the brain, the heart temperature may be too high and the controller may increase the flow rate of the cooling heat exchange assembly, resulting in cool fluid flowing to the brain and ultimately draining into the heart.

After step 944, or if the controller determines in step 942 that the heart temperature is normothermic, the controller determines in step 946 whether the brain temperature is hypothermic. As discussed throughout, cryogenic fluids may be delivered to the cerebral vasculature for therapeutic purposes. In some embodiments, the brain temperature may be between 0 ° and 36 ° C for the cooling therapy. In some embodiments, the target brain temperature for treatment may be about 32-33 degrees Celsius. In some embodiments, the target temperature for treatment may be about 28 degrees celsius. In some cases, the fluid from the cooling heat exchange assembly may be at about 6-10 ℃. In some cases, a higher temperature fluid may be used, such as 15 ℃.

If the controller determines that the brain temperature is not low, via step 948, the temperature of the cooling heat exchange assembly may be adjusted by the controller, via step 946. For example, if the brain temperature is not low enough, the controller may lower the temperature setting of the cooling heat exchange assembly to produce a cooler fluid flow to the brain. In some cases, the controller may determine that the brain temperature is insufficient for therapeutic purposes. For example, the controller may set the heat exchange assembly to, for example, 0-2, and the fluid may ultimately reach the patient at approximately 6-10. In some cases, higher temperatures may be required, for example 15 ℃.

In some embodiments, at step 948, the temperature may be adjusted based on the ratio of the received body temperature and the flow rate of the cold fluid at the set temperature to the cerebral vasculature. In some embodiments, the controller sends commands to the heat exchange assembly to adjust the temperature of the heat exchanger. In some embodiments, the flow rate may be adjusted. For example, the controller 910 of fig. 18A may send instructions to the cooling heat exchange assembly 904 via the I/O path 916 and/or the network interface 920 to adjust the temperature of the heat exchanger 908 and/or set the flow rate of the pump 906.

After step 946, or if the controller determines in step 942 that the brain temperature is (sufficiently) cold, the controller receives new measurement inputs from various sensors. Importantly, if the cooling and heat exchange assembly used to generate the flow of coolant to the brain is adjusted, the heart temperature should be rechecked. Of course, based on the newly received heart and brain temperatures, the controller may again adjust the heat exchange assembly to maintain safe treatment.

Fig. 18C depicts an illustrative flow diagram of a process for adjusting a therapy system using a controller and incorporating two heat exchange assemblies, in accordance with some embodiments of the present disclosure. In this case, the first heat exchange assembly is controlled to cool the fluid flowing to the brain and the second heat exchange assembly is controlled to heat the fluid flowing to the heart. Process 950 includes steps for analyzing the sensor data to determine how to adjust the flow rate and temperature of each heat exchange assembly. Some embodiments may utilize a control engine stored and executed by one or more processors and memory of a controller, such as the controller 910 or other device that performs the steps of the process 950 depicted in the flowchart of fig. 18C. Some embodiments may use process 930 to initially set the temperature and flow rate of the brain cooling therapy system. Some embodiments may use process 930 to maintain and adjust the temperature and flow rate of the brain cooling therapy system.

In step 952, the temperature near the brain is measured. For example, the brain temperature may be measured by the brain temperature sensor 922 of fig. 18A, which may include one or more thermistors placed within the patient. For example, brain temperature may be estimated and/or measured by a proxy, for example, using nasopharynx and/or tympanic temperature probes.

In step 954, the temperature near the heart is measured. The heart temperature can be measured/calculated in a number of ways. For example, the cardiac temperature sensor 924 of fig. 18A may be used. Cardiac temperature sensor 924 may include one or more thermistors, such as thermistors in or on a catheter inserted into the patient, such that the thermistor is located on or near distal tip 205 to allow distal end 204 to be located at or near an atrial boundary and/or the right atrium of the heart. In some embodiments, the heart temperature may be inferred based on the temperature and volume measured for the SVC and IVC, as described above.

In step 956, the rate of fluid flowing near the brain is measured. In some embodiments, the flow rate may be set and/or measured by a pump that is part of a heat exchange assembly used, for example, to cool fluid flowing to the brain. In some embodiments, separate sensors may be used to determine the flow rates in the various veins or arteries.

In step 958, the rate of fluid flowing near the heart is measured. In some embodiments, the flow rate may be set and/or measured by a pump that is part of a heat exchange assembly used, for example, to heat fluid flowing to the heart. In some embodiments, separate sensors may be used to determine the flow rates in the various veins or arteries.

At step 960, the controller receives measurements of brain temperature, heart temperature, and flow rate. In some embodiments, a controller, such as controller 910 of fig. 18A, may receive sensor measurements via I/O path 916 and/or network interface 920.

In step 962, control determines whether the heart temperature is normal. In some embodiments, the heart temperature may be calculated by the controller or by another device prior to transmission to the controller, if not directly measured. For safety reasons it is important that the heart temperature is kept around 36-37 ℃. In some cases, if the heart temperature drops below a certain temperature, for example 32 ℃, all cooling should be stopped immediately and closed urgently, for example if the occlusive element of the catheter contracts accidentally. If the controller determines that the heart temperature is normothermic in step 962, the controller determines whether the brain temperature is hypothermic in step 966. If the controller determines in step 962 that the heart temperature is not normothermic, the controller decides to make an adjustment using steps 972 and/or 976.

In step 966, the controller determines whether the brain temperature is low in step 966. As discussed throughout, cryogenic fluids may be delivered to the cerebral vasculature for therapeutic purposes. In some embodiments, the brain temperature may be between 0 ° and 36 ° C for the cooling therapy. In some embodiments, the target brain temperature for treatment may be about 32-33 degrees Celsius. In some embodiments, the target temperature for treatment may be about 28 degrees celsius. If the controller determines in step 966 that the brain temperature is low enough, the controller receives a new measurement input and the cycle repeats. If the controller determines at step 966 that the brain temperature is low enough, the controller decides to make an adjustment using steps 972 and/or 976.

At step 972, if the controller determines at step 942 that the heart temperature is not normothermic, the flow rate of the warming heat exchange assembly may be adjusted by the controller. For example, if the heart temperature becomes too low, the controller may increase the flow rate of the heating heat exchange assembly, thereby generating a flow of heating fluid to the heart. In some embodiments, the flow rate may be adjusted based on a ratio of the received body temperature and the flow rate of the cold fluid at the set temperature flowing to the cerebral vasculature. In some embodiments, the temperature may be adjusted. In some embodiments, the controller sends commands to the heat exchange assembly to adjust the flow rate of the pump. For example, controller 910 of fig. 18A may send instructions to heat exchanging assembly 905 to set the flow rate of pump 907 via I/O path 916 and/or network interface 920. In some cases, the heart temperature may be too high and the controller may reduce the rate at which the flow rate heated heat exchange assembly produces warmed fluid to the heart. From there, the controller may make other adjustments, for example, in step 972 and/or step 976, or the controller receives new measurement inputs from various sensors in step 960 and repeats the loop.

At step 972, if the controller determines that the heart temperature is not normothermic (step 962), the flow rate and/or temperature of the warming heat exchange assembly may be adjusted by the controller. For example, if the heart temperature is not high enough, the controller may increase the temperature setting of the warming heat exchange assembly to produce a warmer fluid flow to the heart. For example, the controller may set the heat exchange assembly to, for example, 40 ° to 42 ° C. In some embodiments, the controller sends commands to the heat exchange assembly to adjust the flow rate of the pump. The warming flow rate may be increased, for example in increments of 50-75ml/min, until the heart temperature increases minimally, for example 0.1-0.3 ℃. For example, the controller 910 of fig. 18A may send instructions to the heat exchange assembly 905 via the I/O path 916 and/or the network interface 920 to set the temperature and/or adjust the flow rate of the heat exchanger 909. From there, the controller may make other adjustments, for example, in step 972 and/or step 976, or the controller receives new measurement inputs from various sensors in step 960 and repeats the loop.

If, at step 976, the controller determines that the heart temperature is not normothermic (step 962) or the brain temperature is not sufficiently hypothermic (step 966), the flow rate of the cooling heat exchange assembly may be adjusted by the controller in the following manner. In some embodiments, when the heart temperature is not normothermic (step 962), the controller may decrease the flow rate of the cooling heat exchange assembly to produce less cold flow to the brain, which will eventually flow to the heart.

In some embodiments, when the brain temperature is not low enough (step 966), if the brain temperature is not low enough, the controller may increase the flow rate of the cooling heat exchange assembly, thereby generating a cold fluid flow to the brain. The warming flow rate can be increased, for example in increments of 50-75ml/min, until the heart temperature minimally increases, for example 0.1-0.3 ℃, before adjusting the flow rate of the cooling heat exchange assembly, so that the heart temperature will not drop too fast, since the cooling heat exchange assembly will deliver more cool fluid to the brain. This cycle can be repeated until the brain temperature reaches a target for treatment, for example, 32-33 ℃ or 28 ℃ in some cases.

In some embodiments, if the heart temperature becomes too low (e.g., freezing), the controller may decrease the flow rate of the cooling heat exchange assembly, thereby generating a cold fluid flow to the brain. In some embodiments, the flow rate of the cooling heat exchange assembly may be adjusted based on a ratio of the received body temperature and the flow rate of the cold fluid flowing to the set temperature of the cerebral vasculature. Typically, the controller will first adjust the flow rate of the warming heat exchange assembly while the flow rate and temperature of the cooling heat exchange assembly remain unchanged unless the heart temperature does not rise fast enough.

In some embodiments, the temperature of the cooling heat exchange may be adjusted at step 976. In some embodiments, the controller communicates a command to the heat exchange assembly to adjust the flow rate of the pump. For example, the controller can set the heat exchange assembly to, for example, 0-2, and the fluid can ultimately reach the patient at about 6-10. In some cases, higher temperatures may be required, for example 15 ℃.

In some embodiments, at step 976, the controller 910 of fig. 18A may send instructions to the cooling heat exchange assembly 904 via the I/O path 916 and/or the network interface 920 to set the flow rate of the pump 906 and/or adjust the temperature of the heat exchanger 908. From there, the controller may make other adjustments, for example, in step 972, or the controller receives new measurement inputs from various sensors in step 960 and the cycle repeats.

After step 972 and/or step 976, or if the controller determines that the brain temperature is (sufficiently) cold at step 966, the controller receives new measurement inputs from the various sensors at step 960 and the cycle repeats. Importantly, if the cooling and/or heating heat exchange assemblies used to generate the flow of cooling fluid to the brain are adjusted, the heart temperature should be rechecked. Of course, based on the newly received heart and brain temperatures, the controller may again adjust the heat exchange assembly to maintain safe treatment.

In some embodiments, the control system may be used to control the temperature of fluid flowing to, for example, the brain and body. The control system may consist of one or more proportional-integral-derivative (PID) controllers. One or more PID controllers can control the cooling heat exchange assembly and one or more PID controllers can control the heating heat exchange assembly. The PID controller can control the flow rate in the heat exchange assembly, the pressure, temperature of all or a portion of the components in the heat exchange assembly, the rotational speed of the pump in the heat exchange assembly, another similar metric, or some combination thereof. The controllers may operate independently of each other, each having its own inputs and outputs, or may be interdependent.

A PID controller controlling the cold heat exchange assembly may receive one or more sensor measurements as inputs. The one or more sensor inputs may include a temperature input, a pressure input, a flow rate input, or other similar measurements. The temperature input may comprise the temperature of the brain and may be measured using a nasopharyngeal temperature probe, a tympanic temperature probe, an intraparenchymal temperature probe in the brain, or some similar metric as an input metric controlled by the PID. The pressure input may be measured in the first heat exchange assembly or in the patient using a device such as a catheter. The output of the PID algorithm may be an electronic signal. The electronic signal may be an analog voltage. The analog voltage may be 0-5V. This analog voltage may control a motor controller circuit, which in practice may be a circuit that converts alternating current to direct current that may be used to power the motor. The motor may be attached to a pump, such as a pump in the first heat exchanger assembly, and application of the output signal from the PID may control the flow rate of the pump. Increasing the flow rate of the pump in the first heat exchange assembly may result in a decrease in the brain temperature and hence in a decrease in the input value measured by the probe measuring the brain temperature. The PID controller can increase or maintain the level of cold fluid flow until the temperature measured by one or more inputs drops to a previously defined setting. The set temperature may be a temperature known to have a protective effect on brain tissue, for example 32-33 ℃ or lower. The maximum flow rate of the pump may be limited based on a known safe flow rate level, such as 50-300 ml/min.

In some embodiments, a pressure sensor in the first heat exchange loop may be able to trigger a slowing or stopping of the flow in the loop if the pressure exceeds a set threshold, for example, exceeds 400 mmHg. A pressure sensor in the first heat exchange circuit can trigger a slowing or stopping of the flow in the circuit if the pressure drops below a set threshold, for example less than-300 mmHg. The pressure sensor measures a pressure value in the patient's vasculature, such as that caused by catheter infusion in the internal jugular vein, if the pressure is greater than a known safe value, such as 30 mmHg. A pressure exceeding a known safety threshold may trigger a pump deceleration or complete stop immediately after exceeding the safety threshold, or may cause the pump to decelerate or stop only after exceeding the safety threshold for a long time, for example for a time of 5 or 15 minutes for which the value exceeds the threshold. The first heat exchange assembly pump may slow down or stop when the input temperature (e.g., the temperature measured at or near the heart) falls below a known safe value (e.g., 33 ℃).

A PID controller controlling the cold heat exchange assembly may receive one or more sensor measurements as inputs. The one or more sensor inputs may be a temperature input, a pressure input, a flow rate input, or other similar measurements. The temperature input may be the temperature of the heart and may be measured using a temperature probe in a catheter in the patient, fluid aspirated from the patient, or some similar metric, as an input metric to be controlled by the PID. A pressure input may be taken in the second heat exchange assembly. The output of the PID algorithm can be an electronic signal, such as an analog voltage of 0-5V. The analog voltage may control a motor controller circuit, which may be a circuit that converts alternating current to direct current that may be used to power a motor. The motor may be attached to a pump, for example in the second heat exchanger assembly, and application of the output signal from the PID may control the flow rate of the pump. Increasing the flow rate of the pump in the second heat exchange assembly may result in an increase in the heart temperature and thus in an increase in the input value measured by the probe measuring the heart temperature. The PID controller can increase or maintain the flow rate level until the temperature measured by one or more of the inputs increases to a previously defined set point. The set point temperature may be a temperature known to be safe for heart tissue, for example 33-37 ℃. The maximum flow rate of the pump may be limited based on a known safe flow rate level, such as 500-. The pressure sensor in the second heat exchange circuit may be able to slow or stop the flow in the circuit if the pressure exceeds a set threshold, for example above 400 mmHg. The pressure sensor in the second heat exchange loop may be able to slow or stop the flow in the loop if the pressure falls below a set threshold, for example below-300 mmHg. The first heat exchange assembly pump may slow down or stop when the input temperature (e.g., the temperature measured at or near the heart) falls below a known safe value (e.g., 33 ℃).

3.0 methods of Selective target organ therapy

3.1 general methods of Selective therapy (see FIGS. 19, 16)

According to some embodiments, the present disclosure provides methods for selective treatment of a selected location of a body, including using one or more therapy delivery devices and therapy delivery apparatuses. The selected location may be an organ, a group of organs, a tissue, a group of tissues, or a similar anatomical target. Fig. 16 shows a system using a controller that incorporates a catheter for use with a patient. Fig. 19 illustrates a system for selective treatment incorporating a catheter for a patient, according to some embodiments of the present disclosure. In some embodiments, the one or more therapy delivery devices may be a catheter or cannula, which may include an elongated body having one or more lumens, such as an infusion lumen for cooling fluids, an infusion lumen for heating or normothermic fluids, an infusion lumen drug for drugs or otherwise, an aspiration lumen 216, a balloon inflation lumen, a temperature probe receiving lumen, a pressure sensing lumen, and the like, or some combination thereof. One or more lumens may extend longitudinally between proximal end 206 and distal end 204. One such therapy delivery device may be a catheter as disclosed herein. The method of treatment may entail connecting a treatment delivery device to one or more infusion catheters and using the system to deliver treatment to a selected location. The treatment may be fluid infusion, and the fluid may be delivered in an antegrade or retrograde direction. The treatment may also involve extracorporeal treatment of blood, saline, or some similar fluid by a treatment delivery device, such as the treatment delivery system described herein. In general, the infusion lumen or lumens of the infusion catheter or catheters may be used to infuse all types of treatment media, including cryogenic and other antiseptic media, hyperthermic or normothermic heating media, blood products, drugs, medicaments, autologous blood, and the like.

In practice, selective treatment may entail delivery of a therapeutic drug, therapeutic cooling, or oxygenated blood, or any combination thereof, to a selected location, such as the brain; in certain cases, the brain of a stroke patient. The treatment may also require maintaining the temperature of the second selected location (e.g., the heart) at a temperature that is deemed not to pose an inadvertent risk to the patient. The one or more therapy delivery devices can be a catheter or cannula as described herein, and the catheter can be placed in a blood vessel of a patient, such as a blood vessel in the central venous system, e.g., the internal jugular vein. The device may be inserted through the internal jugular vein, and the tip of the device may be located in a vein downstream of the point of insertion, such as the distal region of the internal jugular vein, the brachiocephalic vein, the superior vena cava, the right atrium, or the inferior vena cava. The catheter may be connected to one or more of the one or more outlets of the therapy delivery device, which may be the therapy delivery system described herein. The configuration of the infusion catheter may allow some or all of the flow generated by the therapy delivery system, such as cooled blood, to reach the brain in a selective manner, such as by retrograde or antegrade. The catheter may also allow a second medium (e.g., a warm blood) to flow to the heart. Treatment may include, but is not limited to, retrograde delivery of drugs to the brain using retrograde infusion of cold deoxygenated blood drawn from the suction port 238 of an infusion catheter that may have been cooled extracorporeally to lower the brain temperature to a therapeutic level. The penumbra region of a stroke patient, retrograde delivery of oxygenated blood to the brain of a stroke patient, antegrade delivery of saline, blood, or similar warming media to the heart, or some combination thereof. In some embodiments, the infusion catheter may be placed in the internal jugular vein of a patient who may have recently suffered or may have suffered a stroke using the Seldinger technique, and the expandable obturator may be expanded to occlude the proximal end of a branch of the internal jugular vein. A subclavian vein through which blood may be drawn from the infusion catheter's suction lumen 216 through one or more ports distal to the inflatable obturator; the blood may then be circulated extracorporeally, with some portions cooled, some portions heated, and possibly oxygenated by the therapy delivery system, or some combination thereof, and then each portion injected through an infusion port of a catheter located proximal to the balloon. E.g., an inflatable obturator) for directional delivery to the brain of a patient and through a distal infusion port of an infusion catheter located distal to the balloon for delivery to or near the heart. In the event of an occlusion of the internal jugular vein, retrograde flow may be created from fluid injected through the proximal infusion port retrograde up the internal jugular vein and into the venous sinuses and vasculature of the brain, which may selectively cool the brain temperature below normal body, deliver oxygen, or deliver drugs or other drugs. Cooling may be selective in that the brain temperature may decrease more significantly than the temperature of other parts of the body, such as the temperature measured in the rectum, heart or esophagus. The warming blanket can be used to keep other parts of the body warm. Fluid injected through the distal inlet may be directed to the heart, and the fluid may be heated to maintain a safe temperature of the heart while the brain is selectively cooled by retrograde flow.

The infusion of the treatment medium may be a combination of fluids. To reduce viscosity and thereby increase flow rate, allowing for a more compact device, the blood can be mixed with saline or other crystals after extracorporeal conditioning before being returned to the body. Thus, the cooled saline may be injected, perhaps up to 2L, retrograde to the brain, delivered through the proximal perfusion port as a bolus or as a mixture with cooled blood. Warm saline can be injected, antegrade to the heart, delivered through a distal infusion port as a bolus or as a mixture with a warm blood.

In some embodiments, the system may be established before patient transfer, during patient transfer, after patient transfer, or some combination thereof. For example, the system may be used to deliver therapy, such as cryogenic therapy, to a patient who has arrived at a first medical facility, who may be intending to be transferred to a second medical facility. Treatment, such as neuroprotective treatment of a stroke patient, can begin at a first location, and such treatment can reduce the transfer of the stroke patient from a first medical facility (e.g., a rural emergency room) to a second medical facility, such as an integrated stroke center. Therapy delivery may continue on the vehicle used to transport the patient, which may be an ambulance, car, helicopter, or the like. An operator in a first hub or transport vehicle may first place one or more catheters in a patient's blood vessel, such as the catheter described herein in the internal jugular vein, connect the device to an extracorporeal circuit, and then control the circuit to provide therapy. Sensors may be placed on or in the patient, such as temperature and pressure sensors, to monitor the patient during treatment. The treatment may be monitored from the console and modulated in response to readings from the sensors. The extracorporeal circuit may be an aspect of the system that is regulated by varying the flow rate, the heat transfer rate to the blood passing through, the oxygenation status, or any combination thereof. Treatment may continue until (or after) the patient arrives at the second medical center.

In some cases, the device may be placed in and extend through the internal jugular vein, through the brachiocephalic vein, through the superior vena cava with the distal tip 205 of the infusion catheter in or near the right atrium of the heart. In other cases, the proximal tip of the device may extend through the right atrium into the inferior vena cava, rather than being located in or near the right atrium of the heart. In other cases, the device may not be able to reach the right atrium, and the proximal tip may be located in the superior vena cava. Prior to beginning treatment, the balloon may inflate, blocking the internal jugular vein. The port of the aspiration lumen 216 may be located at or near the junction of the brachiocephalic vein, or in or near the superior vena cava. The suction port 238 may draw all or a portion of the blood returning to the heart from the upper body and provide the drawn blood to an inlet of the therapy delivery system. In this way, cooling fluid that may be retrograde perfused to the brain prior to draining from the contralateral internal jugular vein may be aspirated by the catheter prior to returning to the heart, thereby minimizing the effects of such possibly slightly cooled blood draining from the contralateral jugular vein. In a therapy delivery system, the pumped blood may be cooled, heated, oxygenated, infused with drugs or other agents, or some combination thereof. A portion of the blood in the therapy delivery system may receive one type of modulation, such as cooling to reduce temperature and oxygenation, while another portion of the blood in the therapy delivery system may receive a different type of modulation, such as heating to raise the temperature of the blood or no temperature adjustment to maintain it at or near body temperature. One or more outlets of the therapy delivery system may be connected to one or more inlets of the infusion catheter, and the conditioned blood may be infused back into the body through one or more infusion ports on the infusion catheter. For example, blood that has been conditioned to warm or normothermic by the therapy delivery system may be infused through a distal infusion lumen (flashback lumen) of the infusion catheter, and a blood delivery system that has been therapeutically cooled and possibly oxygenated may be infused through a proximal infusion lumen (cooling lumen) of the infusion catheter. A proximal infusion port or proximal outlet may be located at the proximal end of the balloon in the internal jugular vein, such that fluid inserted through the lumen flows retrograde to the brain. The distal infusion port or distal outlet may be located at or near the tip of the device, in or near the right atrium of the heart, in or near the inferior vena cava, or in or near the superior vena cava, allowing warmed or normothermic blood to flow directly to the heart.

Thus, the system draws some or all of the blood returning to the heart from the upper body, including the cooled blood injected to cool the brain, back from the contralateral vein to the heart. This aspirated blood may be conditioned in two or more parts; one portion of the blood is cooled and possibly oxygenated for retrograde infusion to continue brain cooling, and another portion of the blood is returned to the heart at or above normothermia so that the heart does not experience a severe or dangerous temperature drop while the brain is cooled.

In some embodiments, a second expandable obturator, which may be an elastic balloon, may be disposed on the body of the catheter such that it may partially or completely occlude the superior vena cava to better isolate the aspiration region, above the second obturator, from the retrograde region (counting region), below the second obturator. This may be beneficial in the following cases: the cooled blood draining from the contralateral vein is cooler than desired when reaching the superior vena cava after passing through the venous vasculature of the brain after one infusion of the internal jugular vein. A sufficient amount of blood must be infused through the distal infusion port to account for the reduced natural blood flow through the superior vena cava to the heart with the deployment of the second expandable obturator. Blood may be delivered at a flow rate of 1ml/min to 1500 ml/min.

In some embodiments, blood may be drawn from the inferior vena cava. In another embodiment, blood may be drawn from the femoral vein, the subclavian vein, the cephalic vein, or some other similar vein.

In some embodiments, blood may be delivered to the right atrium. In other embodiments, blood may be delivered to the superior or inferior vena cava.

In some cases, the infusion catheter may be positioned at a venous drainage structure of a target organ, such as the brain, for example, the internal jugular vein. When the inflatable obturator is inflated, there may be one or more outlets, proximal infusion port(s), and pressure port on the target organ side of the inflatable obturator. Both the one or more aspiration ports 238 and the distal infusion port(s) of the infusion catheter may be located on the systemic side of the occlusion, distal to the expanded obturator.

3.1.1 results of a study of Selective retrograde brain Cooling

Us provisional patent application No. 62/947,457, filed 12/2019 and incorporated herein by reference, details a study entitled "selective retrograde brain cooling in complete brain circulation arrest" for use with pig and human cadavers. To establish selective retrograde brain cooling, the method of choice involves unilateral occlusion of the internal jugular vein and application of cold fluid to the head in the area of the occlusion for targeted brain cooling. The perfusate circulates the venous sinuses before exiting the intracranial space through the contralateral internal jugular vein. Normothermic perfusion cadaver studies used catheters that facilitate this method and demonstrated that the flow of chilled perfusate through the venous system did not directly conflict with arterial inflow. The preferential flow of cooling fluid in the low pressure venous system is demonstrated, thereby minimizing the risk of venous engorgement.

In animals that experienced a complete 15 minute cessation of cerebral circulation, the brain temperature reached 29.3 ℃ from 37.6 ℃ after 4 liters of cooled saline was given within 20 minutes. Functionally, the animals were able to eat, drink and walk independently 24 hours after extubation, with a Neurological Deficit Score (NDS) of 26, indicating normal neurological function. The 24-hour functional outcome of animals receiving a complete 30-minute cessation of cerebral circulation was improved over 15-minute animals with an NDS of 10. 6 liters of chilled saline was injected into the animal and brain cooling was from 36.8 to 31.9 ℃. The last animal experienced a complete cerebral circulation stop of 90 minutes and was cooled from 37.4 ℃ to 25.4 ℃. After surgery, the animal developed seizures with a 24 hour NDS of 290, was unconscious and euthanized. The rectal temperature did not drop below 31.5 ℃ for all animals. Endovascular cooling through the internal jugular vein of cadavers resulted in a reduction in brain parenchymal temperature of 19 ℃ in 11 minutes to a depth of 18 ℃. The cooled simulated blood flowed from the administration field of the right internal jugular vein to the contralateral jugular vein, through the dural sinus as evidenced by fluoroscopy. The dura mater, transverse, sigmoid, superior and petrosinus and facial veins fill along this flow path.

Studies of normothermic perfused human cadavers have shown that retrograde cerebral perfusion with targeted brain cooling via a venous catheter placed percutaneously in the internal jugular vein is indeed feasible. Furthermore, the significant speeds (1.73 ℃ for the carcass and 0.42 ℃ for the 15 minute cycle stop pig model) and cooling depths (18 ℃ for the carcass and 25.4 ℃ for the pig model) exceeded those seen in the pig models with similar plant flow rates. While in vivo models have advantages in incorporating metabolic thermogenesis with other factors, the results suggest that cooling through the body vasculature, particularly the dural sinus system, may provide a more facile route to deeper hypothermia.

3.1.2 alternate pulling and pushing

In some embodiments, the extracorporeal system may alternate between aspirating blood through the aspiration lumen 216, delivering warmed blood through the distal infusion port, and delivering cooled blood through the proximal infusion port in response to user input or sensor measurements of physiological parameters. Such alternation may allow for more effective treatment such that blood drawn through the device may be used to cool the brain in one instance, during which time no flashback occurs; in subsequent instances, the blood withdrawn from the device may be used to reverse the temperature of the heart, during which little or no cooling occurs. This cycling can occur in rapid succession and would be useful if the volume and flow rate of blood required for adequate cooling or flashback exceeded reasonable values drawn immediately from the suction port 238 and used for simultaneous brain cooling and cardiac flashback. Furthermore, in some embodiments of the catheter (where one lumen serves as both an aspiration lumen and an anti-hyperthermia lumen), this alternation must occur.

In some methods, the system may be established before or during patient transfer or some combination thereof. For example, the system may be used to deliver therapy, such as cryogenic therapy, to a patient who has arrived at a first medical facility, who may be intending to be transferred to a second medical facility. Treatment, such as neuroprotective treatment for a stroke patient, may begin at a first location, and such treatment may reduce brain damage suffered by the stroke patient during transport from a first medical facility to a second medical facility. Therapy delivery may continue on a vehicle for transporting the patient, which may be an ambulance, car, helicopter, or the like. An operator in a first center or transport vehicle may first place one or more aspiration and reinfusion devices in a patient's blood vessel, such as a single aspiration and reinfusion catheter in the internal jugular vein, connect the device to an extracorporeal circuit, and then open the circuit to begin treatment. Sensors may be placed on the patient, such as temperature and pressure sensors, to monitor the patient during treatment. The treatment may be monitored from the console and modulated in response to readings from the sensors. The extracorporeal circuit may be an aspect of the system that is modulated by varying the flow rate, heat transfer rate to the blood passing therethrough, and the like. Treatment may continue with the patient having reached a second medical center.

3.2 Single catheter infusion

In some embodiments, the therapeutic fluid may be administered through a vein or artery supplying or draining the target organ through an inlet catheter, which may be an infusion catheter as described herein. The flow and characteristics of the flowing fluid in the inlet conduit may be regulated by a therapy delivery system, which may be in fluid communication with the conduit. Temperature sensors may be used in catheters or on the body of a patient to monitor the temperature resulting from cooling, as described in the description of the therapy delivery system. Blood flow through the selected organ may be retrograde or antegrade. If desired, the catheter may include an expandable occlusion element to occlude the vessel. Occluding the vessel may allow retrograde infusion in the vessel. The inlet conduit may be used to deliver drugs or other agents, crystals, colloids, blood products or other treatment media to prevent damage to the selected organ. Where the selected organ is the brain, the reflux created in the internal jugular vein may be used to deliver neuroprotective drugs or other neuroprotective agents, such as calcium antagonists, cell membrane stabilizers, 5-hydroxytryptamine receptor antagonists, xenon, free radical scavengers, or the like to the brain of a patient, such as a patient with ischemic stroke. Retrograde flow may be advantageous because it can reach tissues that are blocked by the clot from receiving normal blood flow, and thus can deliver the administered fluid for therapeutic benefit. It should be understood that the desired flow may be antegrade or retrograde, arterial or venous, and any combination thereof, depending on the target organ or tissue to which the administered fluid is delivered by the infusion catheter.

3.2.1 antegrade approach (see FIGS. 16-21)

In the case of antegrade treatment, the catheter may be placed in an artery that delivers blood to the selected organ. The catheter may be an infusion catheter as described herein, or a device comprising all or part of the features of the infusion catheter. The catheter may enter the body through the carotid artery, the femoral artery, or through a peripheral artery (e.g., the radial artery in the arm), in which case it may be necessary to navigate the catheter to the desired location using a guidewire and fluoroscopic imaging guidance. Fig. 20 shows a system for antegrade treatment using a catheter passed through a patient's carotid artery. Fig. 21 shows a system using antegrade therapy with a catheter passing through a radial artery of a patient, and fig. 22 illustrates a system using antegrade therapy with a catheter passing through a femoral artery of a patient, according to some embodiments of the present disclosure. A therapeutic fluid, such as cooled autologous blood, oxygenated or non-oxygenated or saline, can be infused through the catheter and antegrade to the target organ. In the case of cold autologous blood, the patient's own blood may be drawn from another arterial or venous access site, cooled, oxygenated, and then infused through an infusion catheter.

Fig. 23 illustrates a system using antegrade treatment, where a catheter enters a carotid artery of a thrombectomy patient through a femoral artery, according to some embodiments of the present disclosure. In some embodiments, the brain may be the organ of choice, and the delivered therapy may be hypothermic in nature. In this case, the catheter may be placed in the carotid artery that delivers blood to the brain, or in the artery of the brain itself, especially an artery that may be occluded in the case of an ischemic stroke. In the case of ischemic stroke, this treatment may be used as an adjunct to thrombectomy, where delivery of therapeutic fluid is initiated before, during, or after the thrombectomy and continued for a period of time to maintain a target temperature in the thrombus. Cerebral neuroprotection, which may be at 25-33 ℃ for several hours.

Fig. 24 illustrates a system using antegrade therapy in which a catheter enters the brain of a thrombectomy patient through the femoral artery, according to some embodiments of the present disclosure. In the particular context of ischemic stroke, the device may be advanced into a large blood vessel where an occlusion occurs. A catheter may be placed through the femoral artery in parallel with a device such as a thrombectomy catheter to remove the clot that caused the stroke, and infusion of therapeutic fluid may cool the brain before, during, or after clot removal.

Fig. 25 illustrates a system using antegrade treatment, in which a catheter is passed through a femoral artery into a patient's brain past an obstruction, according to some embodiments of the present disclosure. In some cases, the catheter will advance through the clot before the clot that may have been removed so that cooling of the ischemic core and penumbra can be better achieved to potentially preserve tissue and reduce the risk of reperfusion injury prior to recanalization. The infusion of the therapeutic fluid, which may include colloids, crystalloid fluids, drugs or blood products, may be performed using a control system, possibly cooled to therapeutic levels. The control system may infuse until certain sensor readings are obtained, such as the temperature of a nasopharynx temperature probe, tympanic temperature probe, or a temperature probe in the catheter, indicating that the selected organ has reached the target temperature. The target temperature may be 25-33 ℃.

3.2.2 retrograde approach (see FIGS. 26-30)

In the case of retrograde therapy, an infusion catheter may be placed in a vein draining a selected organ. In one case, the brain may be the organ selected for treatment.

Fig. 26 illustrates a system using retrograde therapy with a catheter via the internal jugular vein of a patient according to some embodiments of the present disclosure. In this case, the infusion catheter may be placed in one of the internal jugular veins that drains blood from the brain. In other cases, the infusion catheter may be placed at other venous access sites, such as the femoral vein, subclavian vein, or cephalic vein, and may be directed to a location where the internal jugular vein or another vein flows retrograde will allow perfusion of the target organ. Fig. 27 shows a system using retrograde therapy, where the catheter is via the femoral vein of the patient. Fig. 28 shows a system using retrograde therapy with a catheter via the subclavian vein of a patient, and fig. 29 illustrates a system using retrograde therapy with a catheter via the cephalic vein of a patient according to some embodiments of the present disclosure. An infusion catheter may be placed in the femoral vein to allow retrograde flow into the brain. Fig. 30 illustrates a system using retrograde therapy in which a catheter is passed through the femoral vein and into the brain of a patient, according to some embodiments of the present disclosure. Infusion catheters may also be placed in the veins of the brain itself.

An expandable obturator, which may be part of an infusion catheter, may be expanded to occlude the internal jugular vein or other vein in which the device may be placed and facilitate retrograde flow of the delivered fluid. The flow and characteristics of the flow fluid in the infusion catheter may be regulated by a therapy delivery system, which may be in fluid communication with the infusion catheter. A therapeutic fluid, such as cooled autologous blood, oxygenated or non-oxygenated or saline, may be infused through the catheter. In the case of cold autologous blood, the patient's own blood may be drawn from another arterial or venous access site, cooled, oxygenated, or both, and then infused through an infusion catheter (described in more detail elsewhere in this document). While the rest of the body may be cooled by such infusion, most of the cooling may occur in the brain as fluid may pass through this region before returning to other parts of the body. The fluid flow path of an expandable obturator infused through a cephalad port to an infusion catheter may be retrograde through the internal jugular vein in which the device may be placed, through the venous sinus and veins of the brain, and thence down the contralateral jugular vein.

In this case, arterial pressure in the arteries and capillaries of the brain may prevent retrograde flow of blood from the veins to the arteries, and thus flow may remain in the venous system. The veins of the brain may act as heat exchangers to achieve rapid, deep nerve cooling. Oxygenated blood, whether normothermic or otherwise, may be delivered retrograde to the brain to supply oxygen to the tissue severed from its supply artery with a quantity of oxygenated blood. Notably, the veins of the brain have more synergy than the arteries of the brain, and thus retrograde blood flow may be more effective than antegrade treatment. When placed in the internal jugular vein, the device may have a lumen that allows it to deliver drugs to the heart, similar to other central venous catheters placed in the central venous system. The insertion method may be the Seldinger technique. Insertion of the treatment device using simple techniques known to all physicians may enable the device to be placed and cooled in hospitals with limited staff and resources (e.g. rural hospitals). In some cases, instead of autologous blood or saline, drugs or other neuroprotective agents may be delivered to the tissue receiving a reduced amount of oxygen in such retrograde methods to slow the rate of cellular damage, for example in acute ischemic stroke patients.

An inverse temperature procedure for keeping the body warm while the brain may be receiving cooling may be implemented. These counter-temperature methods may include the use of a warming blanket, heating pad, forced air heating blanket, or similar warming device. These inverse temperature methods may help to keep the body, particularly the heart, near normothermia, while the brain may be undergoing selective cooling. As described in connection with the therapy delivery system, the temperature sensor may be used to monitor and modulate cooling from the infusion.

3.2.3 retrograde method of saline infusion (see FIGS. 27-34)

Fig. 31 illustrates a system using retrograde therapy using saline infusion through a catheter through the internal jugular vein of a patient according to some embodiments of the present disclosure. In some cases, cooling saline or other crystalloid fluids may be used to cool all or part of the body tissue. The patient's blood dilution may be monitored so that their blood is not diluted to dangerous levels during the infusion of saline. In one instance, saline may be injected retrograde through the device in the internal jugular vein. In such cases, an inflatable obturator may be used to redirect retrograde flow of saline. Saline can be injected at temperatures above 0 ℃ and below 37 ℃ and the brain can be selectively cooled.

In some embodiments of such saline infusion methods, blood may be aspirated from a separate lumen in the same device as the infusion lumen or from a different device located in another vessel of the body to prevent excess blood volume. Fig. 32 illustrates a system using retrograde therapy using saline infusion pumped from the femoral vein through a catheter through the internal jugular vein of a patient. Fig. 33 shows a system using retrograde therapy using saline infusion through a catheter of the patient's internal jugular vein and aspiration from the internal jugular vein. These methods may be used to rapidly adjust the patient's brain temperature to a lower level, which may be desirable during an emergency ischemic event (e.g., stroke and cardiac arrest). The lens fluid may be delivered by bolus injection, sequential bolus injection, or continuous flow.

In some embodiments, the present disclosure provides a method of using retrograde flow to assist in removing an obstruction in a blood vessel. Fig. 34 illustrates a system using retrograde therapy using saline infusion and a catheter that uses reverse flow to remove clots, according to some embodiments of the present disclosure. Retrograde flow may be provided by the infusion catheter. The flow may also have a cooling fluid that may be used to cool the surrounding area of the occlusion container. Retrograde flow may exert forces on clots lodged in the blood vessels, such as in cerebral arteries, which may help remove clots in the blood vessels. If an arterial occlusion is being removed using a suction catheter or stent-embolectomy, the reverse flow may provide additional force to help remove the clot and may provide additional benefits such as delivering neuroprotection or therapeutic drugs to the affected brain portion for stroke.

Fig. 35 shows a system using retrograde therapy using saline infusion and catheter to remove clots during thrombectomy, while fig. 35 shows a system using retrograde therapy. Fig. 36 illustrates a system using retrograde therapy during embolectomy using saline infusion and a catheter using retrograde flow cooling, according to some embodiments of the present disclosure. In some embodiments, a thrombectomy catheter, such as an aspiration catheter or a stent retrieval catheter, may be used with a retrograde cooling method. A thrombectomy catheter may be inserted into the femoral artery and directed to the clot in the brain, while retrograde cooling may be delivered through the catheter at the jugular vein or other venous location.

In some embodiments, the infusion catheter may be connected to a source or infusion, such as a source of saline or blood, for direct infusion, and may be administered with the aid of a pressure bag for immediate delivery of the therapeutic fluid. Figure 37 illustrates a system for retrograde therapy using saline infusion via a catheter of the internal jugular vein of a patient according to some embodiments of the present disclosure;

fig. 38 illustrates a system for retrograde therapy utilizing a catheter to deliver a drug to the brain according to some embodiments of the present disclosure. In some embodiments, the infusion catheter may deliver a neuroprotective drug or other neuroprotective agent to the proximal end of the inflatable obturator so that the flow of the drug or agent may be directed retrograde toward the brain. The flow rate of the infusion may be adjusted based on input from the sensor or changes in the patient's state of the vessel occlusion. The retrograde route of administration may better reach the ischemic portion of the brain that has experienced an ischemic stroke, and thus may deliver neuroprotective agents better than the antegrade route. The neuroprotective agent or other neuroprotective agent may be a calcium antagonist, a cell membrane stabilizer, a 5-hydroxytryptamine receptor antagonist, xenon, a free radical scavenger, or the like.

3.3 extracorporeal Circuit

3.3.1 aspiration and infusion in the same device (see FIGS. 35-41)

The present disclosure provides a method for aspirating blood, conditioning the blood ex vivo, and then re-infusing the blood to deliver a treatment, particularly a cryogenic treatment, targeted to a particular organ or group of organs. Blood may be drawn through one or more catheters and re-infused through one or more catheters. The reinfusion method may be any of the antegrade or retrograde infusion methods described herein. The one or more catheters may comprise an infusion catheter as described herein. It should be noted that when used in this method, the infusion catheter should contain aspiration and infusion lumens. The aspiration lumen 216 may be larger than the reinfusion lumen to ensure that stable flow may be achieved in the extracorporeal circuit. The surface area of the aspiration lumen 216 may be 1.25 to 3 times larger than the reinfusion lumen to promote stable flow. In vitro modulation may be accomplished by a therapy delivery system as described herein or a similar system with some or all of its components. This selective treatment method using one or more devices connected to an extracorporeal circuit can be used to treat ischemic stroke patients. In any stroke patient, the treatment may be used before, during or after the thrombectomy, or independent of the thrombectomy. Treatments such as cooling may allow for a longer treatment eligibility time window in which the patient may receive additional treatment for the stroke. Sensors, such as temperature sensors described in association with therapy delivery systems, may be used to monitor therapy, such as cryogenic therapy.

In some methods, the system may be established before or during patient transfer, or some combination thereof. For example, the system may be used to deliver therapy, such as cryogenic therapy, to a patient who has arrived at a first medical facility, who may be intending to be transferred to a second medical facility. Treatment, such as neuroprotective treatment for a stroke patient, may begin at a first location, and such treatment may reduce brain damage suffered by the stroke patient during transport from a first medical facility to a second medical facility. Therapy delivery may continue on the vehicle used to transport the patient, which may be an ambulance, car, helicopter, or the like. An operator in the first center or transport vehicle may first place one or more aspiration and reinfusion devices in a patient's blood vessel, such as a single aspiration and reinfusion catheter in the internal jugular vein, connect the device to the extracorporeal circuit, and then open the circuit to begin treatment. Sensors may be placed on the patient, such as temperature and pressure sensors, to monitor the patient during treatment. The treatment may be monitored from the console and modulated in response to readings from the sensors. The extracorporeal circuit may be an aspect of the system that is modulated by varying the flow rate, heat transfer rate to the blood passing therethrough, and the like. Once the patient has reached the second medical center, treatment may continue.

In some cases, the method for aspirating and reinfusing blood may be the same device. The device may be a central venous catheter, placed in the internal jugular vein of a patient. Fig. 39 illustrates a system for treatment using a catheter configured to aspirate fluid in the internal jugular vein and return fluid in the internal jugular vein of a patient. The device may draw blood from near the vena cava junction or some other location along the catheter body, condition the blood extracorporeally, and then re-infuse the blood into the internal jugular vein or other location where the device may be placed. The device may also be placed in the femoral vein, subclavian vein, cephalic vein or some similar vein. Fig. 40 illustrates a system for retrograde therapy in which the catheter is configured to aspirate fluid in the femoral vein and return fluid in the internal jugular vein of a patient. Fig. 41 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in the subclavian vein and return fluid in the internal jugular vein of a patient. Fig. 42 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a cephalic vein and return fluid in an internal jugular vein of a patient, and fig. 43 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a femoral vein and return fluid in a cerebral vein of a patient, according to some embodiments of the present disclosure. The suction port and the infusion port may be separated in the vessel by an inflatable obturator (e.g., balloon). The infusion port may exit at the proximal end of the balloon such that the flow rate out of the port is retrograde to the brain. Extracorporeal regulation may include cooling of the blood, heating of the blood, oxygenation of the blood, infusion of drugs into the blood, etc., and may be accomplished by a therapy delivery system. The device may be placed using the Seldinger technique. The system may continuously withdraw and re-infuse blood in response to sensor measurements of physiological parameters, or may adjust the flow rate through the extracorporeal circuit. The system can be pulled out and re-infused with blood after balloon inflation. Sensors, such as those described in connection with the therapy delivery system, may be used to monitor therapy. Physiological parameters that may be measured by the sensor include heart temperature, which may be measured by a proxy near the interatrial junction via a temperature sensor, particularly a thermistor, infusion pressure, which may be measured on an infusion catheter using a pressure port proximal to the inflatable obturator, brain temperature which may be measured non-invasively using a tympanic temperature sensor or a nasopharyngeal temperature sensor. If the measurement from one of these sensors indicates that the system may need to be modified, if the heart temperature is too low, the infusion pressure is too high, or the brain temperature is too high, for example, the system may adjust the flow rate, such as increasing or decreasing the temperature of the reinfused blood, increasing or decreasing the flow rate of the reinfused blood, increasing or decreasing the oxygenation of the reinfused blood, completely stopping the flow through the extracorporeal system, or the like.

In some embodiments, the device may be an infusion catheter as described herein placed in an internal jugular vein. The device may aspirate blood from at or near the luminal interface, deliver the blood to the therapy delivery system described herein, where the temperature, flow rate, oxygenation, or some combination thereof may be modified, and then re-infuse the catheter through the perfusion lumen at the time of infusion. A distal temperature sensor may monitor the heart to ensure that the reinfused blood does not cool the heart to dangerous levels.

In another case, aspiration and re-injection may be performed in the same device, but the flow may be antegrade rather than retrograde. The infusion catheter may enter the femoral artery, carotid artery, brachial artery, or the like and be directed to a location near or in the cerebral artery, near the ischemic stroke site. Fig. 44 shows a system for antegrade treatment, where the catheter is configured to aspirate fluid in the femoral vein of the patient and return the fluid to the arteries of the brain. Fig. 45 illustrates a system for antegrade treatment in accordance with some embodiments of the present disclosure, wherein the catheter is configured to aspirate fluid in the femoral vein of the patient and return the fluid to the carotid artery. Autologous blood may be drawn from an infusion catheter or from a different access site of the body (e.g., the femoral artery). Where the infusion catheter includes two or more lumens, the suction port 238 may be disposed proximal of the infusion port at or near the device distal end 204, and the proximal suction port 238 may suction blood from other vessels, such as the aortic arch or descending aorta through which the device passes. The aspirated autologous blood may be treated by cooling, oxygenation, or cooling and oxygenation. After treatment, autologous blood can be returned directly to the brain via the outlet of the infusion catheter to the area affected by the stroke. This injection of cold fluid directly into the brain can cool the brain to therapeutic levels, which can have the significant benefit of hypothermia.

3.3.2 aspiration and infusion in different devices (see FIGS. 46-55)

In some cases, a first device may be used to draw blood from a first location, while a second device may be used to reinfuse blood at a second location. The reinfusion site may be in a vein to create retrograde flow in combination with an inflatable obturator on a device, as described herein, such as a device in the internal jugular vein.

Fig. 46 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a femoral vein of a patient and to return fluid in an internal jugular vein, according to some embodiments of the present disclosure. The return site may also be by one of the venous retrograde methods described herein, such as by a catheter placed in the femoral vein, subclavian vein, cephalic vein, or other venous vessels. Fig. 47 illustrates a system for retrograde therapy, where the catheter is configured to aspirate a fluid in a femoral artery of a patient and to return the fluid into a femoral vein. Fig. 48 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a femoral vein of a patient and to return fluid in a subclavian vein, according to some embodiments of the present disclosure.

The reinfusion device may also be in an artery using one of the arterial antegrade flow methods described herein, such as the internal carotid, femoral, radial, or other arterial vessels. Fig. 49 illustrates a system for antegrade treatment, wherein the catheter is configured to aspirate fluid in the femoral vein of a patient and to return fluid to the carotid artery. Fig. 50 illustrates a system for antegrade treatment, wherein a catheter is configured to aspirate fluid in a femoral vein of a patient and to return fluid in a radial artery. Fig. 51 illustrates a system for antegrade treatment in which a catheter is configured to aspirate fluid in a femoral artery and to return fluid in a radial artery of a patient, according to some embodiments of the present disclosure.

The suction location may be at any one or more of a plurality of locations in the body; it can be placed anywhere a vascular access can be established to draw blood. Fig. 52 illustrates a system for antegrade treatment, where the catheter is configured to draw fluid from any vein of a patient and to return the fluid into the femoral artery. Common access points include femoral vein or artery, radial artery, subclavian vein, internal jugular vein, carotid artery, cephalic vein, radial artery, etc., or any combination thereof. It will be appreciated that any combination of one or more access points for aspiration may be used with any delivery point or points for reinfusion, even though all permutations are not shown.

In some embodiments, a suction device may be placed in the femoral vessel, flow may be suctioned to flow through an extracorporeal circuit where it may be adjusted by cooling, oxygenation, flow rate changes, etc., and then re-infused by a reinfusion device placed in the internal jugular vein. Fig. 53 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a femoral vein and to return fluid in an internal jugular vein of a patient, according to some embodiments of the present disclosure. In such cases, the expandable obturator may occlude the internal jugular vein distal to the outlet of the return catheter, which may cause retrograde flow to the brain to provide selective treatment. Common access points include femoral vein or artery, radial artery, subclavian vein, internal jugular vein, carotid artery, cephalic vein, radial artery, etc., or any combination thereof. Fig. 54 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a cephalic vein of a patient and to return fluid in an internal jugular vein, according to some embodiments of the present disclosure.

In another embodiment, the aspiration device and the reinfusion device may be separate lumens in the same device, such as through the femoral vein into the body and may be directed to the internal jugular vein. Navigation of the catheter may utilize a guidewire for proper placement of the device.

In some embodiments, the aspiration device may be placed in the internal carotid artery and the infusion device may be placed in the internal jugular vein. Fig. 55 illustrates a system for retrograde therapy in which a catheter is configured to aspirate fluid in a patient's carotid artery and to return fluid in an internal jugular vein, according to some embodiments of the present disclosure. In this case, the extracorporeal circuit may not require a pump, as the pressure differential between the carotid artery and the jugular vein may be sufficient to cause retrograde flow to the brain through the internal jugular vein. This blood transfer method may be used to retrograde deliver oxygenated blood to the brain of a patient. Blood from the carotid artery can be cooled either in vitro or in vivo.

In practice, the extracorporeal circuit may have a heat exchanger that cools the blood to a temperature of 0 ℃ or higher. The pump may adjust its flow rate in the range of 0-5L/min, for example, based on a tympanometry sensor or other sensor, which may serve as a proxy for brain temperature or another organ temperature. The system may have a heat exchanger that cools the blood to 0 ℃, which may be autologous. The pump may adjust its flow rate in the potential range of 0-5L/min, for example, based on the distal tip 205 (as a proxy for body temperature) from the tympanic temperature and catheter temperature sensors as representative of brain temperature.

In another embodiment, blood may be diverted directly from an artery or vein to an infusion catheter, possibly with temperature modulation in vivo. Thus, arterial blood may be accessed from, for example, the carotid artery and infused cephalad into the inflatable obturator, without passing through an extracorporeal regulation system, thereby providing oxygenated blood to the brain. In addition, in vivo cooling as described herein may be used to cool the shunted blood prior to infusion into the brain.

3.4 closed-loop organ compartmental therapy (see FIGS. 56A-56B)

In some embodiments, the therapeutic fluid may be administered to one or more target organs through a vein or artery through one catheter at a first location, referred to as an inlet catheter, for selective treatment, and then aspirated up by another catheter at a second location, referred to as an outlet catheter. Blood flow through the selected organ may be retrograde or antegrade. One or both of the inlet and outlet conduits may be infusion conduits as described herein. If desired, the inlet and outlet conduits may include one or more expandable occluders to occlude the vessel.

3.4.1 antegrade pathway

Fig. 56A illustrates a system for antegrade closed loop therapy according to some embodiments of the present disclosure. In the case of antegrade treatment, the first location may be in an artery supplying blood to the selected organ, and the second location may be in a vein draining the selected organ. In one case, the brain may be the organ that is selected to be cooled, and the inlet catheter may be placed in one or both of the carotid arteries that deliver blood to the brain. Therapeutic fluid, such as cold autologous blood or saline, may be infused through these catheters to selectively cool the brain. In one or both internal jugular veins, i.e., the veins that drain blood from the brain, an outlet catheter may be placed to withdraw cold drainage fluid from the brain to prevent cooling elsewhere in the body. The outlet conduit may be an infusion conduit as described herein. Anatomical locations of the catheter may include femoral arteries, peripheral arteries, such as the radial artery, carotid artery, and the like; and the catheter can be navigated to the target artery by these methods.

3.4.2 reverse path

Fig. 56B illustrates a system for retrograde closed loop therapy according to some embodiments of the present disclosure. In the case of retrograde therapy, the first location may be in a vein draining the selected organ, while the second location may be in an artery supplying blood to the selected organ. In one case, the brain may be the organ that is selected to be cooled, and the inlet catheter may be placed in one or both of the internal jugular veins that drain blood from the brain. An expandable obturator, which may be a feature of an infusion catheter, may be expanded to occlude the internal jugular vein and facilitate retrograde flow of fluid to the side of the injection head to the occlusion. Therapeutic fluids, such as cold crystals or cooled autologous blood, can be injected through these catheters, which can selectively cool the brain. For example, in one or both carotid arteries, or in the contralateral internal jugular vein, an outlet catheter may be placed to aspirate fluid expelled from the brain. The outlet conduit may be in communication with an extracorporeal heater cooler device to reheat the fluid prior to its reinfusion to the body. In this way, the cooled fluid is delivered to the target organ, e.g., the brain, but is removed when flowing out of the target organ, and may be reheated and re-infused to potentially minimize systemic cooling. In the case of an outlet catheter placed in the contralateral jugular vein, only one inlet catheter would be placed. The outlet catheter in the contralateral jugular vein may be an infusion device as described herein, or may be a simple catheter without an inflatable obturator. If present, the inflatable obturator on the exit device may prevent the therapeutic fluid from reaching the rest of the body, so that all of the therapeutic fluid may be aspirated through the exit conduit. The flow path may be retrograde through the internal jugular vein in which the device may be placed, through the venous sinuses and veins of the brain, and out the contralateral internal jugular vein which may be drained through an outlet catheter. In this case, arterial pressure in the arteries and capillaries of the brain may prevent retrograde flow of blood from the vein through the vein to the artery, and thus the injected fluid may flow to the contralateral internal jugular vein.

If a catheter with an occluding member is used, the occluding member may be expanded to completely isolate the organ from the rest of the bodily circulation, thereby allowing closed flow to the selected organ. If a catheter without an occlusion element is used, the outlet catheter can draw fluid out of the body fast enough so that minimal cold fluid from the infusion lumen passes through the target organ area. This may allow for selective cooling of the brain without cooling the heart or other organs. In some cases, the system may deliver oxygenated blood or therapeutic drugs rather than a therapeutic coolant, such as cooled autologous blood or cooled saline. In certain areas of treatment where neuroprotection may be required and the brain is the target organ, for example in ischemic stroke, delivery of a neuroprotective agent such as a calcium antagonist, a cell membrane stabilizer, xenon, a 5-hydroxytryptamine receptor antagonist or a free radical scavenger or the like may be delivered. The pressure at which the drug or agent may be infused may depend on the severity and location of the occluded vessel, requiring higher pressure to reach clots in more distal locations in the brain.

Although one inlet conduit and one outlet conduit are discussed, it should be understood that multiple infusion or inlet and aspiration or outlet conduits may be used to achieve selective cooling of the organ. The required number may be determined based on the number of relevant inflow and outflow vessels to the selected organ to be cooled.

3.5 application in thrombectomy (see FIG. 57)

Fig. 57 illustrates a treatment system for use in a thrombectomy procedure, according to some embodiments of the present disclosure. In some embodiments, a system is described that can open a blood vessel containing an obstruction and control the temperature of blood at a specified location. The system may include a first catheter 266 that may be used to open an artery containing an occlusion, such as an artery in the brain or heart, temperature control elements, sensors, and a treatment circulatory system. The first catheter 266 for opening the occluded artery may be an aspiration catheter or stent retriever for thrombectomy procedures. The temperature control element may also have one or more heat exchange elements 245, which may be disposed on the catheter body 202. Heat exchange member 245 may be expandable and may be filled with a circulating fluid. The circulating fluid may be cooling water, brine or other coolant fluid.

The temperature control element may be in thermal communication with blood flowing through the element in the container, and may allow cooling of such fluid flowing through the temperature control element. Sensors, such as temperature, flow rate or pressure sensors, may be used to monitor changes in the responsive temperature control element. The temperature sensor may be disposed on a catheter intended to open an occluded artery, may be external to the patient being treated, may be internal to the patient being treated, or may be on a catheter remote from the temperature control element in the blood vessel. A temperature sensor on the catheter used to open the occluded vessel or on the catheter distal to the temperature control element may be used to sense the temperature of the fluid that has passed through the temperature control element. Internal and external temperature sensors located on the patient undergoing treatment may be placed to monitor the temperature of the patient's body as the temperature control element changes the temperature of the fluid in the body vessel. For example, tympanic membrane temperature, nasopharyngeal temperature, or internal jugular vein temperature may be monitored by sensors to track temperature changes at these locations. The temperature sensor may be in communication with the treatment circulation system. The therapy circulation system may control the pressure, flow rate, or temperature of the fluid circulating through the temperature control element. Input from the temperature sensor may be used to adjust a flow rate, pressure, or temperature parameter of the fluid circulated by the therapeutic circulatory system through the temperature control element. A control system may be used to allow the therapeutic circulation system to modulate the temperature of a target portion of the body (as measured by one of the temperature sensors) to a level that may be therapeutic, for example a therapeutic hypothermia in the range of 25-36 ℃.

3.6 internal heat exchanger (see FIG. 58)

In some clinical situations, such as reducing brain damage during ischemic events including ischemic stroke, cooling may be required for neuroprotection. The cooling may be performed by locally cooling blood, a crystal or another fluid (working fluid) flowing through the lumen of the catheter device. The cooling conduit may include a flexible conduit having a lumen for delivering the working fluid to the target organ, and one or more coolant tubes lumens that may be in thermal contact with the working fluid lumen. The catheter may allow for the passage of interventional tools, such as devices used for thrombectomy or angioplasty, to accomplish methods of using the devices during thrombectomy or angioplasty. The catheter may be used with a cooling circuit system that may include a control module, a pump, a heat exchanger, a flow circuit connecting the pump and the heat exchanger, and a catheter, such as the therapy delivery system described herein. A pressure, temperature, or flow rate probe may be in the fluid flow circuit and may be used to measure the cooling state of the fluid in the conduit or the cooling state of the body. The cooling state of the body can be measured by a temperature sensor on the patient's body, such as a nasopharynx or tympanic temperature sensor. These temperature sensors may be placed on or in the human body. These sensors may be in communication with a control unit, which may use these measurements to determine the flow rate of the pump and the amount of heating/cooling to be delivered to the working fluid. The pump may move the fluid, the heat exchanger may heat or cool the fluid, and the control unit may adjust the flow rate and heat exchange capacity of the pump.

In some embodiments, a conduit arrangement may be used with the cooling circuit system. Fig. 58 illustrates a system for treatment with a catheter configured as an intrabody heat exchanger according to some embodiments of the present disclosure. The device may be placed in the venous or arterial system. After device placement, the device may be navigated to a location for selective sexual organ cooling. Navigation may include navigation of blood vessels using a guidewire and continuous X-ray (fluoroscopy) to place the device in position for selective organ cooling. The organ of choice may be the brain, which may be selected because it may be suffering ischemic injury and would benefit from neuroprotective hypothermia. A catheter may be placed in the carotid artery so that blood flow from the device flows directly to the brain. The fluid cooling circuit pump can be activated such that cold fluid circulates within the device in one or more internal cavities in thermal contact with the working fluid channel. The working fluid, whether cold saline, cold blood, or cooled and oxygenated blood, may be pumped through the working fluid channel and delivered to the selected organ. A cooling circuit may be used to keep the working fluid cool before it is discharged at the tip of the catheter. Such treatment may be maintained for a long period of time, e.g., 2-12 hours, with the control system monitoring variables such as temperature and pressure. The catheter may also include a balloon to anchor it in place and prevent it from moving during operation. The balloon may be occlusive to prevent flow to all or part of the selective organ.

In some cases, blood may be withdrawn from a first location, cooled in vivo, and then reinfused at a second location at a lower temperature. Active cooling of the blood may be performed as the blood flows through one or more lumens of the intracorporeal catheter. Cooling may be accomplished using heat exchange surfaces in thermal communication with one or more lumens carrying a cooling fluid. The heat exchange surface may have coolant circulating in other lumens of the catheter or may have elements arranged outside the catheter that allow cooling of the fluid in the lumens. The externally disposed element may be a balloon in which a coolant fluid may be circulated. For example, an aspiration catheter may be placed in the femoral artery, and an infusion catheter may be placed in the internal jugular vein. A body circuit connecting the aspiration and return catheters in the body may drive blood flow from the artery to the internal jugular vein. There may be an additional channel in the in-vivo regulating device that allows circulation of cold fluid that is in thermal communication with the blood passing through the in-vivo regulating device. The cold fluid can cool blood passing through the body circuit, thereby lowering the temperature as the blood is delivered to the internal jugular vein. This allows administration of oxygenated frozen blood that can be used to reduce brain damage in stroke patients. In some cases, the conduit may require additional length to facilitate additional cooling of the fluid passing through the conduit.

3.7 impeller tube (see FIGS. 59A and 59B)

Fig. 59A illustrates an embodiment of a conduit having an impeller in accordance with some embodiments of the present disclosure. The catheter body 202952 is depicted in fig. 59A as having a proximal end 206946 and a distal end 204948. In some embodiments, catheter body 202948 may be inserted into a patient's vasculature to create an occlusion in the internal jugular vein and to create a flow of cold fluid proximally and a flow of cold or hot fluid distally. For example, the catheter body 202948 can be inserted with the distal end 204948 positioned in the patient's superior vena cava or right atrium to direct normal or high temperature fluids to the patient's heart and the proximal end 206946 can be positioned in the patient's internal jugular vein to create retrograde flow of cryogenic fluid in the patient's cerebrovascular system. The catheter body 202952 produces a cold fluid output at the proximal end 206946 and a hot fluid output at the distal end 204948.

Separate proximal 206946 and distal 204948 ends are an inflatable occlusion element 944 and a cuff (cuff)/one-way valve 966. An inflatable occlusion element 944, typically an inflatable balloon, is secured to an outer surface of the elongate catheter body 202952, the inflatable occlusion element 944 may assume an inflated configuration and a deflated configuration, typically comprising a balloon structure that is fluidly connectable to a source of inflation fluid, such as saline. As the catheter body 202952 is inserted intravenously into a patient, the expandable occlusion element 944 can expand to occlude blood flow outside of the catheter body 202952.

In the catheter body 202952, distal to the inflatable occlusion element 944 and cuff 966 is a lateral port 964 that allows fluid/blood to flow in. In some embodiments, as fluid enters the lateral port 964, the fluid may flow proximally through the cuff 966. The fluid may be pulled proximally by the proximal impeller pump 958. The cooling wall 954 cools the fluid as the fluid moves proximally. Cold fluid may be output through the proximal end 206946 to produce a cryogenic fluid stream, for example, into the patient's cerebral vasculature.

In some embodiments, fluid may flow distally as it enters the lateral port 964. Fluid may be pulled distally by the distal impeller pump 960. The heated wall 956 heats the fluid as it moves distally. The warmed fluid may be output through the distal end 204946 to create a flow of normal or high temperature fluid, such as to the patient's heart.

The cooling wall 954 and the heating wall 956 may be cooled/heated in various ways. For example, each wall may be made of a conductive material, separated from each other by a non-conductive barrier, and cooled or heated, respectively. In some embodiments, each wall may be filled with a cooled or heated fluid, respectively. In some embodiments, the cooling wall 954 and the heating wall 956 may have additional insulating and/or safety coatings. Each of the proximal propeller pump 959, the distal propeller pump 961, the cooling wall 954, and the heating wall 956 may be powered by, for example, an on-board battery and/or an extracorporeal circuit.

In some embodiments, one or more temperature probes may be incorporated in the catheter body 202952. For example, a thermistor or other sensor may be placed at the proximal end 206946 or the distal end 204948. The catheter may include a controller, such as a controller. The temperature data from the temperature sensors is collected with a processor and memory and the flow rate is adjusted by each of the proximal impeller pump 958 or the distal impeller pump 960, as well as the temperature of the cooling wall 954 or the heating wall 956.

In some embodiments, the elongated impeller pumps 958 and 960 can be replaced with

smaller pumps

959 and 961. Fig. 59B illustrates an embodiment of a catheter with a propeller, according to some embodiments of the present disclosure. Each of the proximal and distal propeller pumps 959, 961 may be powered by, for example, an on-board battery and/or an extracorporeal circuit.

In some embodiments, in the catheter body 202952, distal to the inflatable occlusion element 944 and cuff 966 is a lateral port 964 that allows for fluid/blood inflow. As fluid enters the lateral port 964, the fluid may flow proximally through the cuff 966. Fluid may be pulled proximally by the proximal propeller pump 959. The cooling wall 954 cools the fluid as it moves proximally. Cold fluid may be output through the proximal end 206946 to produce a cryogenic fluid stream, for example, into the patient's cerebral vasculature.

In some embodiments, fluid may flow distally as it enters the lateral port 964. Fluid may be pulled distally by the distal propeller pump 961. The heated wall 956 heats the fluid as it moves distally. The warmed fluid may be output through the distal end 204946 to create a flow of normal or high temperature fluid, such as to the patient's heart.

4.0 catheter methods of use

4.1 Limb perfusion (see fig. 60)

Some embodiments may include a method for treating a patient including introducing a catheter into an arterial vasculature of the patient, for example, during extracorporeal membrane oxygenation. In some embodiments, the infusion catheters described herein may be placed in the vasculature of a patient, possibly in the superficial femoral artery. Fig. 60 illustrates a system for treatment using a catheter configured for limb perfusion, according to some embodiments of the present disclosure. The device may be used to selectively occlude the vasculature by deploying an inflatable obturator outside of a catheter within the superficial femoral artery of a patient. In this particular case, occluding the superficial femoral artery of the patient may help to maintain blood flow from the common femoral artery to the deep femoral portion, helping to perfuse the patient's limb. The device may be similarly placed in the common femoral artery and may be navigated to the superficial femoral artery for occlusion and infusion.

4.2 carotid endarterectomy (see FIG. 61)

The systems and devices described herein may also be used to selectively cool the brain during carotid endarterectomy, where plaque may be removed from the carotid arteries. As shown in the figure. Fig. 61 illustrates a system for treatment using a catheter during carotid endarterectomy according to some embodiments of the present disclosure. This process may involve a temporary ischemic event during which cooling may be beneficial for neuroprotection. As described herein, selective retrograde nerve cooling, neuroprotection using oxygenated blood or drugs, etc., can be used to mitigate the potential risks of this procedure. In addition, placement of the device in the setting of carotid endarterectomy may be performed by surgical incision upon visualization of the internal jugular vein, rather than by percutaneous methods.

5.0 automated catheter Placement (see FIGS. 62-63)

A fully or partially automated system for inserting a fluid delivery device into a fluidic system is described herein. This system may be referred to as an automatic insertion system. The fluid delivery device may be an arterial or venous catheter, such as the perfusion catheter described herein. The fluid system into which the device may be inserted may be a blood vessel of the human body. The fluid delivered may be a therapeutic medium, a drug, a crystal, a colloid, a blood product, and the like. The automated components of the system may include algorithms for identifying regions on the medical imaging data to identify relevant structures in the fluid system. Further automation components may include articulated insertion mechanisms that may assist in placing a device for delivering fluid to a fluid system, or may be fully capable of placing a device for delivering fluid to a fluid system. The system may be used to enable percutaneous access of veins and arteries in a variety of environments, particularly for non-conventional arrangements of percutaneous access, particularly outside hospitals.

In some embodiments, the device for delivering fluid may be an arterial or venous catheter. The catheter may be an infusion catheter including an elongate catheter body 202, the catheter body 202 having one or more lumens. The flow of various media described herein may be through the lumen of the device. The device for delivering fluid may have an inflatable obturator that may be used to occlude a blood vessel in a fluid system. The catheter may be an infusion catheter as previously disclosed, or a similar catheter with an inflatable obturator, but it should be understood that there are iterations of the device that do not contain an inflatable obturator. One or more lumens may be used to deliver the fluid. The device may have a tapered tip to enable the device to be placed through an orifice by an automated insertion system. The device may have adhesive or other non-invasive attachment methods to the outer surface. For example, the catheter may have an adhesive coated portion that can be used to secure the catheter to the patient's body, thereby eliminating the need to suture the device to the patient's skin.

In some embodiments, the fluid system in which the automated insertion system places the device may be a blood vessel of a human body. The blood vessel may be a vein or an artery. When inserted into the venous system, the device may be inserted into the central vasculature, such as the internal jugular vein, femoral vein, or similar insertion site, or into the peripheral vasculature, such as the subclavian vein, cephalic vein, or similar insertion site. In some cases, a device placed in a vein may be able to occlude blood flow in the normal direction, for example by using an expandable occlusion element, and in the event of occlusion of the normal flow direction, flow through the device may be directed against the vena cava system. When inserted into the arterial system, the device may be inserted into the central vasculature, such as the internal carotid artery, femoral artery, or similar insertion point, or into the peripheral vasculature, such as the brachial artery, radial artery, or similar insertion point. When placed in an artery, flow through the device may be directed in an antegrade direction. Both antegrade and retrograde venous flow may be used for selective cooling of one or more target organs.

In practice, the device may be a central venous catheter placed in the internal jugular vein. In another instance, the device may be an infusion catheter as described herein and may be used to cool the brain by blocking flow in the internal jugular vein with an inflatable obturator and directing the flow of cooling fluid to the brain.

In some cases, the fluid delivered may be a therapeutic medium, a drug, a crystal, a colloid, a blood product, and the like. The mechanism on the insertion catheter may be capable of directing the flow path of the delivered fluid. For example, a catheter having an expandable occlusion element may occlude a vein in which it may be placed, thereby promoting retrograde flow in the vessel. The delivered fluid may be temperature modulated to cause cooling or warming of all or a particular area of the fluid system. Temperature regulation of the fluid may be accomplished by a heat exchanger. The delivered fluid may be delivered by the therapy delivery systems disclosed herein, or by systems having some or all of the same features. The flow of the delivered fluid may be driven by a pump or pumping mechanism. The pump may be small enough to fit in an ambulance and may have a volume of between 0 cubic feet and 5 cubic feet. The delivered blood may be oxygenated and may be oxygenated by an external oxygenator. The delivered fluid may be delivered by the therapy delivery systems disclosed herein, or by systems having some or all of the same features.

In some cases, an automated element of the system may include an algorithm for identifying the medical imaging region. Figure 62 illustrates a system for automated catheter placement using, for example, ultrasound, in accordance with some embodiments of the present disclosure. The algorithm may be used to identify relevant structures in the fluid system. The relevant structure may be a blood vessel of the human body, such as the internal jugular vein. The identified blood vessel may be a blood vessel in which the fluid delivery device is to be placed. The medical imaging used may be ultrasound, computed tomography or fluoroscopy. The algorithm may utilize computer vision to identify the relevant structures. The algorithm may be a deep learning algorithm that may have been trained on the labeled medical imaging scan data set and may be able to identify relevant structures with high accuracy. The deep learning algorithm may be a clustering algorithm, an object detection algorithm, or similar algorithms that may identify structures on a video or picture. A convolutional neural network may be implemented to identify relevant structures on the medical imaging data. The output of the algorithm may include directions and instructions to the user, and the output may be displayed on a screen of the console. The guidance and instructions may include instructions regarding an optimal placement location for inserting the fluid delivery device into a body vessel, a suggested angle of insertion into a vessel, a force or velocity of penetration into a vessel, or similar instructions to facilitate proper placement, which may enable the device to be placed semi-autonomously and by a medical professional other than a physician. Alternatively, the output of the algorithm may be used as an input to an articulated insertion mechanism to allow it to place the fluid delivery device into the blood vessel completely autonomously.

Indeed, the medical imaging algorithm may analyze a real-time stream of ultrasound data from the ultrasound probe. The algorithm may be used to identify the internal jugular vein in order to identify the insertion location of the central venous catheter. The algorithm may identify the internal jugular vein or other relevant blood vessels on the screen. The operator may then be given instructions on the screen as to the optimal position, angle, force, speed, or some combination thereof to use when inserting the centerline. Alternatively, the output of the algorithm may be used as an input to an articulated insertion mechanism to allow it to place the fluid delivery device into the blood vessel completely autonomously.

In some embodiments, the automated element may include an articulated insertion mechanism that may assist in placing or be fully capable of placing a device for delivering fluid to the fluid system. Fig. 63 illustrates a system for automated placement of a catheter including an articulating insertion mechanism according to some embodiments of the present disclosure. The hinged insertion mechanism may be controlled by a control system. The articulating insertion mechanism may be a robotic inserter that is movable in at least 1 degree of freedom to align with an insertion point on the body. The articulated insertion mechanism control system may be computer numerically controlled, which may control the feed rate, positioning and speed of the articulated insertion mechanism. The articulating insertion mechanism may have means for holding a fluid delivery device (e.g. a catheter, such as a central venous catheter) in a first position outside the fluid system, and the means may be capable of moving the fluid delivery device to a second position so that it may be inserted into the fluid system through the aperture. The fluid system may be a blood vessel of the human body, such as the internal jugular vein. Placement of the device may follow a technique similar to the Seldinger technique in which venous access may be established by needle puncture, the skin may be opened slightly with a small incision, a guidewire may be placed, and a dilator may be used as needed to prepare the vessel for placement of the device prior to introduction of the device through the guidewire into the vessel. In some cases, the means for holding the fluid delivery system may be a linear retraction mechanism that can advance or retract the fluid delivery device, which may be a central venous catheter placed in the linear retraction mechanism. The orifice may be a hole or perforation in the skin of the patient and the fluid system may be a vein of said patient. The control system of the articulated inserter may take input from the algorithm used to identify the medical imaging region to determine the optimal insertion point for the fluid delivery device. The hinged insertion mechanism may include mounting features that allow it to be secured to an external structure. The external structure may be a human body and the articulating insertion mechanism may be anchored to a specific location near the target vessel in which the fluid delivery device may be placed. The mounting features may allow for stabilization and calibration of the articulating insertion mechanism to allow the insertion mechanism to always insert the device into a particular location, which may be a particular location on the person's body. Before the fluid delivery device can be inserted, a placement probe, such as a needle, may first be used to pierce the fluid system and ensure that the fluid delivery device is placed in the correct area of the fluid system. Sensors such as pressure sensors, flow rate sensors, or temperature sensors may be used to detect when a placement probe or fluid delivery device may have been successfully placed into the fluid system. In the case where the fluid system is a human blood vessel, the sensor may detect a flow rate, a pressure change, or a temperature change when the fluid delivery system (e.g., a catheter) penetrates the blood vessel. The puncture may produce a flash of blood flow from the high pressure system (e.g., a blood vessel) to the low pressure system (e.g., a catheter), and the flash may indicate when a probe or fluid delivery device has been successfully placed in the correct container or has not been successfully placed in an incorrect container. The control system may use the input from the sensor to determine whether the fluid delivery device has been properly placed in the fluid system and therefore does not require substantial movement, or whether the fluid delivery device has not been properly placed in the fluid system and therefore requires substantial movement.

Indeed, the articulating insertion element may carry a catheter, possibly a central venous catheter, attached to a linear actuator to retract and extend the catheter for insertion into the central venous system. The auxiliary actuation system may be capable of moving in 1 or more degrees of freedom to control the feed rate, position and angle of the linear actuator. The assistance system may take input from an algorithm for identifying the medical imaging region and position the linear actuator at a point identified as being most appropriate for placing the catheter into the vein. The control system may control and coordinate the movement of the linear actuators and the auxiliary systems, and may also take input from sensors that detect when the catheter or placement probe may have entered the correct blood vessel in the body. The sensor may detect a pressure or flow rate reading that is too high for the venous system, in which case the device may be located in the artery and the control system may remove the placement probe or catheter and reposition it in the correct vessel.

The system may be used to enable percutaneous access of veins and arteries in a variety of settings, particularly for non-conventional settings of percutaneous access, particularly outside hospitals. EMT, nurses, or similarly trained medical professionals may use the system at the scene of an accident or during transport to a hospital. The system can be used to place devices percutaneously in an ambulance on the way to a hospital. The device may be placed on a stroke patient to provide therapy to potentially reduce brain damage incurred during transport. The system may also be used in the field of accidents to provide treatment as soon as possible after an accident has occurred. In some cases, a person without medical training may be able to place the system on a patient. In these cases, the automation of the system allows a less skilled physician to begin providing therapy before the patient arrives at the hospital. In addition to the treatment of extrahospital stroke, this method can also be used to treat or arrest of the heart or traumatic brain injury, as well as other ischemic or traumatic events.

Lavage for Central temperature management

Additional devices are disclosed and described herein that are intended to help maintain body temperature near normothermia during retrograde cooling infusion in the neck for targeted brain hypothermia. If the temperature inversion mechanism described in the above-described infusion catheter may fail to achieve the desired brain-body temperature difference level, it is recommended that the body be selectively heated using an add-on device while allowing the brain to continue to cool.

The use of gastric lavage as a means of central temperature management has previously been demonstrated in low temperature animal models; brunette et al. The 1987 study showed that gastric lavage as a rewarming method was much slower than thoracic lavage with warm solution. Theoretically, this may be due to the relatively small surface area to volume ratio of the stomach, and the relatively thick and well vascularized walls of the stomach. However, while this will prove to be a significant limitation in rewarming hypothermic patients, these anatomical features may allow the stomach to be a perfect organ for maintaining the desired core temperature. The location of the stomach relative to the inferior vena cava and the location of the diaphragm (so to speak, mediastinum) may also help to maintain central intravascular temperature prior to or during localized hypothermia.

The multi-lumen lavage tubes described herein can be used as an adjunct in central temperature management. Figure 64 illustrates a treatment system incorporating a gastric lavage for central temperature management according to some embodiments of the present disclosure. The lavage tube comprises a multi-lumen device having proximal and distal inflatable occluders, otherwise referred to as occlusion balloon(s). The lavage tube is designed with a sufficiently large outer diameter, perhaps 36 Fr. The tube may have an outer sheath to allow proximal and distal movement. Secured to the sheath body is a proximal inflatable obturator. Fig. 65 illustrates a system and outer sheath for treatment incorporating gastric lavage for central temperature management in accordance with some embodiments of the present disclosure. The proximal inflatable obturator will serve to seal off the gastroesophageal junction and prevent heated contents from flowing back into the esophagus.

A distal inflatable obturator secured to the body of the lavage tube allows pyloric occlusion. The radiopaque tip allows for placement of the tube under fluoroscopic and/or ultrasound guidance. The distal port(s) 240 allow for the initiation of the inflow of warm solution prior to or at the time of localized brain hypothermia. A temperature probe may be placed in one port to additionally measure the intragastric temperature accurately, or in some embodiments may be incorporated into the lavage tube itself.

The nearest port (strategically placed distal to the proximal inflatable obturator) will allow for aspiration of the perfusate and transfer to the heat exchanger to reheat and return to the stomach cavity, allowing for maintenance of a constant inner lumen temperature. Additional embodiments of such a lavage tube can contain lumen(s) at the exit proximal end of the proximal balloon (within the esophagus) for placement of an esophageal temperature probe and/or aspiration of esophageal contents to minimize the risk of aspiration. Another iteration may include an additional lumen exit distal to the pylorus at the distal end of an expandable obturator for enteral feeding in cases where long term placement of the lavage tube is required.

Given the risk of aspiration, the use of such a lavage tube may require a tracheal tube, a large volume of warmed perfusate to fully distend the stomach and reach the desired temperature, and radiographic aids to ensure proper positioning of the tube.

Administration of warmed fluid through a lavage tube can include crystals, blood products, drugs, or combinations thereof. According to the present canine study data, these fluids can be safely delivered through a lavage tube in the 39-40 ℃ range for the purpose of temperature inversion of the body during or before targeted brain hypothermia treatment.

While the techniques described herein may be used for performing hyperthermia during local hypothermia, alternative uses may include maintaining core hypothermia when needed, as an adjunct to active rewarming using other techniques, and for delivering heated chemotherapeutic agents in the treatment of esophagogastric tumors.

Insulated guide catheter and related methods of use

According to some embodiments, the present disclosure provides an insulated guide catheter that includes an elongate catheter body 202, the elongate catheter body 202 having one or more lumens extending longitudinally between a proximal end 206 and a distal end 204. Fig. 66 depicts an exemplary exterior view of an insulated guide catheter, and fig. 66 depicts an exemplary exterior view of an insulated guide catheter. Fig. 67 depicts an exemplary cross-sectional view of an insulated guide catheter, according to some embodiments of the present disclosure. The elongate catheter body 202 can have an access lumen that allows one or more additional devices to pass through it, such as a thrombectomy catheter, a guidewire, or other devices that can be placed coaxially. The channel lumen may also allow passage of a fluid, which may be a cooling fluid, in addition to or instead of the attachment means. The conduit may have an insulating layer which helps prevent the cooling fluid flowing through the conduit passage from heating up. The insulation material may be an aerogel or aerogel-based material, or some other similar insulation material. Aerogel materials can be effectively insulated using the knudsen effect. The body of the catheter may be made of a polymer. The wall of the polymeric body may comprise reinforcement, for example from coiled or braided wire. The reinforcement may provide kink resistance, column strength, hoop strength, or similar advantageous mechanical properties to the catheter. The coiled or braided wire may be stainless steel, nitinol, Liquid Crystal Polymer (LCP) or some similar reinforcing material. The conduit may have an active cooling feature that actively reduces the temperature of the fluid flowing through the conduit. One such active cooling feature may be one or more lumens that may be used to circulate a fluid, such as a cooling fluid, within the catheter, which may cause cooling or maintain the temperature of the fluid flowing through the channel. The one or more lumens for circulating fluid may receive fluid input from one or more inlet ports at the proximal end 206 of the device and output fluid from one or more outlet ports at the proximal end 206 of the device. The one or more fluid circulation lumens may direct fluid longitudinally from the one or more proximal inlets to the distal end 204 of the device, and at the distal end 204 of the device, the fluid may reach a direction change point where the fluid may change direction and flow longitudinally to the proximal end 206 of the device, where it may be expelled through the one or more outlet ports. The fluid flowing through the circulation lumen may be water, air, a refrigerant such as R-134A, or some similar fluid. The cross-sectional shape of the circulation lumen may be circular, arcuate, oval or some other cross-sectional shape.

The size of the cross-sectional area may taper longitudinally, e.g., the cross-sectional area may be larger at or near the proximal end 206 of the catheter, and the cross-sectional area may be smaller at or near the distal end 204 of the catheter. Fig. 68 depicts an exemplary cross-sectional view of an insulated guide catheter near each of the proximal end 206 and the distal end 204, according to some embodiments of the present disclosure. Alternatively, the cross-sectional area may be smaller at or near the proximal end 206 of the catheter and the cross-sectional area may be larger at or near the distal end 204 of the catheter. The insulated guide catheter may have a tip that may allow insertion of the device into a blood vessel without damage. The tip may be atraumatic and may allow the catheter to enter a blood vessel, such as a blood vessel of a human body, to minimize trauma upon insertion. The tip may also be radiopaque so that it is visible when used in conjunction with medical imaging (e.g., X-ray or fluoroscopy). The distal end 204 of the catheter may also comprise a distal flexible length, which may allow it to be atraumatically navigated through a blood vessel, such as the human vasculature. The catheter may contain one or more sensors to evaluate one or more parameters of the fluid in the catheter, the fluid in the channel, or the environment surrounding the catheter. These sensors may include temperature, pressure, flow rate sensors, and the like. These sensors may allow for measurement of the outlet velocity of the fluid flowing through the channel, the outlet temperature of the fluid flowing through the channel, the pressure of the fluid flowing through one or more channels. The circulation lumen, the temperature of the fluid flowing through the circulation lumen, the ambient temperature, or some similar parameter. The sensor may have an electrical connector that may be at or near the proximal end 206 of the device, which may allow the device to exchange signals with an external system such as a cooling console system.

An insulated guide catheter may be placed in a blood vessel, vein or artery of a patient, and may be used to deliver therapy. Fig. 69 illustrates a system for treatment incorporating an insulated guide catheter, in accordance with some embodiments of the present disclosure. The tunnel lumens may be used for infusion of all types of media including cryogenic, normothermic, hyperthermic and other temperature modulation media, blood products, drugs, medicaments, autologous blood, and the like. The catheter may be placed within a neurovascular support catheter. One example of such a neurovascular support catheter includes stroker flowgate2 or penumbraneuromax. In a preferred embodiment, the insulated guide catheter has an outer diameter of between 0.07-0.09 inches, preferably 0.081 inches, to enable it to be installed in either a FlowGate2 or neuro max088 neurovascular support catheter. The device may be used to inject a cooled fluid into the body. Fluid may be injected through the channel lumen of the device, and one or more active cooling features may circulate the cooled fluid to cool or maintain the temperature of the fluid injected through the channel. The insulation may allow both the circulating fluid in the circulation lumen and the fluid injected through the channel to be maintained at a lower temperature than the environment surrounding the device. The device may be placed in the human body and may be used as a guide catheter for other medical devices, such as a thrombectomy catheter, a guidewire or similar medical devices. The guide catheter may enter the body through the femoral artery or some similar arterial access point. It may be used in conjunction with or in place of a teleflex guidieline et al guide extension catheter. The device may be placed in the femoral artery and navigated to the Common Carotid Artery (CCA) or Internal Carotid Artery (ICA), or some other artery of the body. In some embodiments, the device may be used to reduce brain temperature during thrombectomy, for example, by selectively cooling the brain. The cooled fluid may be injected through the device, exiting at the distal end 204 of the device, and entering an artery, such as the common carotid artery or the internal carotid artery, and the injected fluid may then flow anterogradely to the brain. When performing a proximal aspiration thrombectomy, the device may be used with or as a balloon guide catheter. When performing a distal aspiration thrombectomy, a balloon guide catheter may not be needed, or the device may not need to function as a balloon guide catheter. The device may be used to apply a cooled fluid after removal of the clot or prior to removal of the clot. The cooling fluid may be administered initially prior to clot removal and continued after clot removal. In some embodiments, the device may be used to cool the heart during a myocardial infarction.

The proximal portion of the device, the portion of the device that may be external to the human body during use, may be connected to a device, such as a cooling console, that circulates cooled fluid through the active cooling features of the catheter, such as a lumen for circulating fluid. Fig. 70 illustrates a system for treatment incorporating an insulated guide catheter and a cooling console, according to some embodiments of the present disclosure. The cooling console may provide a cooled fluid to an inlet of a lumen of the device that circulates the cooled fluid throughout the device. The console may also provide an outlet for the input fluid after it has circulated through the system. The cooling console may feature cooling fluid prior to insertion of the fluid into the conduit inlet. These cooling features may be a cooling circuit that uses a heat exchanger to reduce the temperature of the fluid. The cooling console may also be an inflow source of fluid injected through the channel lumen, intended to be expelled at or near the distal end 204 of the device. The cooling console may have one or more pumps that allow fluid to move throughout the system. The cooling console may have one or more control units that may allow a user to monitor parameters of the system and may allow the user to modify the performance of the system, such as by changing settings. The cooling console may be in communication with one or more sensors of the device, and the output of these sensors may be displayed on the cooling console, e.g., on a control panel. If the measurements received from one or more of the one or more sensors of the equipment are outside of a specified range, the cooling console may modify its performance, such as by using a control module, or notify the user to modify its performance. The pump, when directed by the control module, is operably coupled to the control module to modify a fluid flow rate through the apparatus. The cooling console, in combination with the insulated catheter, can be used to deliver cryogenic fluids to the body, which can be used to treat reperfusion injury or ischemia of the brain or heart.

The system may also be inserted through a vein, such as the femoral vein, and may be used to deliver cooled fluid retrograde. In this embodiment, the guide catheter may have a balloon to block flow in the venous system and allow for delivery of retrograde flow.

Reversible catheter embodiment

Fig. 71-73 illustrate an iv catheter device 10 including an elongated hollow catheter body 12 extending between a proximal end or hub 14 and a distal end 16. The iv catheter 10 is also provided with at least one outer inflatable balloon 18 secured to the outer surface of the elongate catheter body 12 and at least one inner inflatable balloon structure 20 secured to the inner surface of the elongate catheter body 12. The elongated catheter body 12 is provided with: an input port 22 located at the proximal hub 14; an output port 24 at the distal end 16; and a transverse port 26 located on the wall of the elongate catheter body 12.

The outer and

inner balloons

18 and 20 are each fixed at a respective location along the length of the elongate catheter body 12, and the lateral ports are positioned at given locations along the length of the elongate catheter body 12 such that the lateral ports 26 are located between the outer balloon 18 and the proximal hub 14 of the elongate catheter body 12 and between the inner balloon 20.

The proximal hub of the elongate catheter body 12 can be fluidly connected to a fluid source, such as a fluid or other antiseptic medium, and the elongate catheter body 12 is adapted to propagate fluid received from its proximal hub 14 along its length, typically through the axial or central lumen 13, and deliver the fluid through the output port 24 and the transverse port 26. At least a portion of the elongate catheter body adjacent the distal end 16 and including the lateral port 26 is insertable into a conduit, such as a vein of a subject.

The outer balloon 18 is inflatable such that it can be changed between a deflated state or configuration and an inflated state or configuration. Similarly, the inner balloon 20 is inflatable such that it can change between a deflated state or configuration and an inflated state or configuration. It should be understood that the outer and

inner balloons

18 and 20 shown in fig. 1 and 2 may be the outer and

inner balloons

18 and 20. Each of fig. 71 to 73 is in a contracted state or configuration. As described below, the size and shape of the outer and

inner balloons

18 and 20 are selected such that the outer balloon 18 occludes the space between the elongate catheter body 12 and the venous lumen into which the iv catheter 10 is inserted, and when in the inflated configuration, the inner balloon 20 blocks the lumen 13 of the elongate catheter body 12 and such that the outer balloon 18 allows fluid to flow in the space between the elongate catheter body 12 and the catheter, and the inner balloon 20 allows fluid to flow within the elongate catheter body when in the deflated configuration.

When the outer and

inner balloons

18 and 20 are in the deflated configuration, fluid injected into the elongate catheter body 12 via the input port 22 flows into the elongate catheter body 12, while some fluid exits the elongate catheter body 12 via the input port 22. The side port 26, while the remaining fluid exits the elongate catheter body 12 through the output port 24.

Fig. 74-76 illustrate the iv catheter 10 when the

balloons

18 and 20 are in the inflated configuration. The outer balloon 18 is inflated around the circumference of the outer surface of the elongate catheter body 12. The diameter of the outer balloon 18 when inflated is selected to be inserted adjacent the inner wall of the catheter into which the iv catheter 10 is entering. As a result, no fluid can flow from the proximal hub 14 of the elongate catheter body to the exterior of the distal end 16 thereof. As shown in fig. 75 and 76, the inner balloon 18, when inflated, encloses the lumen of the elongate catheter body 12 such that no fluid can flow within the lumen 13 of the elongate catheter body 12 from its proximal hub 14 to its distal end 16.

As a result, when the outer and

inner balloons

18 and 20 are inflated, any fluid injected into the elongate catheter body 12 via the input port 22 is blocked by the inflated inner balloon 20 and thus cannot flow down to the distal output port 24, also referred to as a drug or infusion outlet. As a result, fluid exits the elongate catheter body 12 through the lateral port 26. After exiting the elongate catheter body 12, the fluid cannot propagate outside of the elongate catheter body 12 toward the distal end 16 of the elongate catheter body 12 because of the inflated outer balloon 20. As a result, fluid flows from the lateral port 26 to the exterior of the elongate catheter body of the proximal hub 14 of the elongate catheter body 12.

It should be understood that the outer and

inner balloons

18 and 20 may each be fluidly connected to a fluid source (not shown) for inflating the

balloons

18 and 20. For example, the fluid source may be adapted to deliver a pressurized fluid (e.g., air or water, typically saline) into the

balloons

18 and 20 to inflate the

balloons

18 and 20. In one embodiment, the fluid source is further configured to draw fluid from the

balloons

18 and 20 in order to deflate the

balloons

18 and 20. In one embodiment, a source of inflation medium, such as a saline filled syringe (not shown), may be connected to an inflation luer or other connector 23 to deliver inflation medium simultaneously to the outer and

inner balloons

18 and 20 through a common inflation port 19 formed in the wall of the elongate catheter body 12. Typically, an axial inflation lumen (not shown) will also be formed in the wall of the elongate catheter body 12 to communicate inflation media from the connector 23 to the common inflation port 19.

Although in the illustrated embodiment the hollow body 12 has a tubular shape, it should be understood that the body 12 may be provided with any other suitable cross-sectional shape, such as an elliptical cross-sectional shape.

While in the illustrated embodiment the inner and

outer balloons

20, 18 are positioned at substantially the same longitudinal location along the length of the elongate catheter body 12, it should be understood that the

balloons

18, 20 may be positioned at different longitudinal locations so long as the outer and

inner balloons

18, 20 are positioned between the distal end 16 of the elongate catheter body 12 and the transverse port 26.

In one embodiment, the elongate catheter body 12 is made of a flexible material. For example, including but not limited to radiopaque polyurethane, silicone, polyethylene, polyvinyl chloride, polytetrafluoroethylene, nylon, or materials that have good interaction with whole blood and its components (e.g., red blood cells, platelets, and inflammatory mediators).

Although in the above description, the outer balloon 18 has a cylindrical shape when in the deflated and inflated configuration, it should be understood that the balloon 18 may have an oval, irregular, or tulip-shaped or other configuration in order to optimize the retrograde flow path of fluid adjacent the inflatable obturator, so long as it can be inflated to seal against the inner wall of the vein when inflated. Generally, the outer balloon 18 may be formed, in whole or in part, of an elastomer or other compliant material to promote compliance and sealing with the inner vessel wall.

While the inner balloon structure 20 is illustrated as a pair of opposing D-shaped kiss balloons in order to meet and occlude the inner lumen 13 of the elongate catheter body 12 when inflated, as illustrated in fig. 76, it will be appreciated that the balloons may have any of a number of specific configurations that will provide complete lumen occlusion when inflated.

The iv catheter 10 may include more than one outer balloon 18 and/or more than one inner balloon structure 20. The number, location, and shape of the outer balloon(s) 18 are selected such that no fluid can flow into the space around the elongate catheter body 12 between the proximal end 14 and the distal end 16 of the elongate catheter body 12 when the outer balloon 18 is inflated. Similarly, the number, location, and shape of the inner balloon structures 20 are selected such that no fluid can flow through the inner lumen 13 of the elongate catheter body 12, and in particular to prevent fluid from flowing from the inlet port 22 to the outlet port 24 at the distal end of the elongate catheter body 12.

While the above description refers to a single source of inflation fluid for inflating both the outer and

inner balloons

18 and 20, it should be understood that the outer balloon 18 may be connected to a first source of inflation fluid and the inner balloon 20 may be connected to a second and different source of inflation fluid.

In an alternative embodiment (not shown), the elongate catheter body 12 does not include the output port 24. In this case, the distal outlet port 24 of the elongate catheter body 12 is closed end such that fluid exiting the iv catheter 10 from the input port may exit the elongate catheter body 12 into the elongate catheter body 12 only through the lateral port 26. In such a case, the iv catheter 10 may not include the inner balloon 20 but only the at least one outer balloon 18.

While the above description refers to a single transverse port 26, it should be understood that the elongate catheter body 12 may be provided with a plurality of transverse ports having any suitable shape and size distributed along the side wall of the elongate catheter and similarly, the elongate catheter body 12 may be provided with more than one output port, the location, shape and size of which may vary, as long as the output port is located at or between the distal end 16 of the elongate catheter body 12. A distal end 16 and an inner balloon 20.

In other embodiments, an intravenous infusion catheter such as catheter 10 may be used as a central venous catheter to provide access to the right atrium for drug delivery and to provide retrograde brain perfusion in emergency situations, such as cardiopulmonary arrest, stroke, cardiac surgery during which the heart is intentionally stopped, or the like. In this case, as shown in fig. 77, the iv catheter 10 is introduced percutaneously into the patient's internal jugular vein 30 and brachiocephalic vein 25, also known as the innominate vein, such that the distal outlet 24 is positioned over the right atrium 27 of the patient's heart 32. The external port 26 remains in the internal jugular vein 30, while the external balloon 18 is located at the interface between the internal jugular vein 30 and the brachiocephalic vein 25. Typically, both the outer and

inner balloons

18 and 20 will remain deflated and the intravenous infusion catheter 10 can be used in the usual manner as a central venous catheter with drugs and other substances delivered to the right atrium 27 through the inlet 22. However, if the patient is suffering from a cardiopulmonary or other emergency, the outer and

inner balloons

18 and 20 will be inflated to alter the flow path through the catheter so that antiseptic media can be injected through the inlet port 22 to exit the side ports 26 and flow in a retrograde direction through the internal jugular vein 30 into the cerebral vasculature to protect the brain tissue from damage during cardiac arrest, as described below.

When used as a central venous catheter, the

balloons

18 and 20 remain in their deflated configuration, and the proximal hub 14 of the intravenous infusion catheter 10 is fluidly connected to a fluid source to direct a first fluid (e.g., a preservative) toward the heart of the subject. Examples of preservative fluids include a crystal solution, blood, oxygenated blood, oxygen-carrying fluid, gel, or the patient's own blood. Examples of drugs that may be delivered include fluids, blood products, and nutritional media.

The distal portion of the iv catheter 10 is inserted into the subject's internal jugular vein 30 such that the port 26 of the elongate catheter body 10 is located within the internal jugular vein 30, and once in place, the iv catheter 10 is secured to the subject. Once the catheter has been installed in the subject's internal jugular vein 30, the fluid source can be activated to deliver the first fluid. The first fluid reaches the input port 22 and propagates into the elongate catheter body 12. The first fluid then exits the elongate catheter body 12 via the lateral port 26 and the output port 24 before propagating to the heart 32.

If an emergency situation is detected, for example when the heart and/or lungs are stopped, the intravenous infusion catheter 10, already in place in the subject's body, may be used to perfuse the subject's brain. To this end, the outer and

inner balloons

18 and 20 are inflated using an inflation fluid source. When inflated, the inner balloon 20 substantially sealingly blocks the passage within the elongate catheter body 12 such that fluid within the lumen 13 of the elongate catheter body 12 does not propagate from the input port 22 to the distal end 16 of the elongate catheter body 12 and out of the elongate catheter body 12 through the output port 24. Fluid from the input port 22 will be redirected (diverted) to exit the elongate catheter body 12 only through the lateral ports 26.

When inflated, the outer balloon 18 extends in the space between the outer surface of the elongate catheter body 12 and the inner wall of the internal jugular vein 30 and abuts the inner wall of the jugular vein 30 to substantially sealingly occlude the passageway between the outer surface of the elongate catheter body 12 and the inner wall of the internal jugular vein 30. Thus, fluid exiting the elongate catheter body 12 through the lateral port 26 cannot propagate toward the heart 32 due to the inflated external balloon 18, and may then propagate in the opposite direction toward the brain.

In one embodiment, a second fluid, different from the first fluid, may be delivered once the outer and

inner balloons

18 and 20 have been inflated. In this case, the proximal hub 14 of the iv catheter 10 is fluidly connected to a second fluid source.

In another embodiment, the same fluid, i.e., the first fluid, may be delivered to the brain after the outer and

inner balloons

18 and 20 are inflated.

In one embodiment, the second fluid to be delivered to the brain after inflation of the outer and

inner balloons

18 and 20 comprises a crystalloid fluid. Such crystalline fluids can cool and protect the brain, and are commonly available in Intensive Care Units (ICU). In an emergency, a non-specialist, such as a nurse, may then inflate the outer and

inner balloons

18 and 20, connect the catheter to a source of crystalloid fluid to the proximal hub 14 of the iv catheter 10, and direct the crystalloid fluid to the brain of the subject.

In another embodiment, the second fluid may be an oxygen-carrying fluid such as blood.

It should be appreciated that any suitable means may be used to fluidly connect the outer and/or inner

inflatable balloons

18 and 20 to at least one source of inflation fluid. For example, a first catheter or conduit may have a first end connected to a first source of inflation fluid and a second end fluidly connected to the outer balloon 18. The first catheter is then located outside of the elongate catheter body 12. The second catheter is inserted into the catheter or tube in the elongate catheter body 12 having a first end connected to a second source of inflation fluid and a second end fluidly connected to the inner balloon 20.

Fig. 78 and 79 illustrate another configuration for fluidly connecting the outer and

inner balloons

18 and 20 to a source of inflation fluid. In this embodiment, a single catheter 40 is used to fluidly connect the inflation fluid source to the outer and

inner balloons

18 and 20. In this embodiment, the wall of the elongate catheter body 12 is provided with an extending lumen 42 along a cross-section from a proximal location adjacent the proximal hub 14 to a distal location facing the outer and

inner balloons

18 and 20. The catheter 40 is inserted into the cavity 42 through a proximal port present in the elongate catheter body 12. The distal end of catheter 40 is fluidly connected to the outer and inner balloons for delivery of inflation fluid thereto.

Fig. 80 and 81 illustrate an embodiment of a catheter configured for simultaneous delivery of two fluids. For example, the catheter may be used to deliver a first fluid to the heart of a subject and a second fluid to the brain of the subject. The catheter does not include an internal balloon, but rather includes a catheter 50 having a distal end connected to the lateral port 26 from the interior of the elongate catheter body 12 and a proximal hub connectable to a source fluid. As a result, when fluid is injected into the elongate catheter body 12 through its proximal port, the fluid exits the elongate catheter body 12 through the distal port. As fluid is injected into the catheter 50, the fluid exits the catheter through the lateral port 26.

In one embodiment, the catheter may be used to simultaneously provide a first fluid to the heart and flush the brain of a subject. The catheter was inserted into the internal jugular vein as described above. The elongate catheter body 12 may be used to deliver a first fluid to the heart of a subject by injecting the first fluid through a proximal port of the elongate catheter body 12. In an emergency situation, the outer balloon 18 is inflated and a second fluid is injected via the catheter 50. The second fluid exits the conduit via the lateral port 26. The second fluid flows in the opposite direction to the brain of the subject because the inflated outer balloon 18 prevents the second fluid from propagating toward the heart of the subject. It will be appreciated that the first fluid may still be delivered to the heart while the second fluid is delivered to the brain of the subject.

Another exemplary catheter device 20, as shown in fig. 82A-82B and 82A-82B, 83A-83D, includes an elongate catheter body 102 having a distal end 104 and a proximal end 106. As shown in fig. 83A-83D, the elongate catheter body 102 includes an infusion lumen 108, an inflation lumen 110, a first drug lumen 112, and a second drug lumen 114. Each lumen has a corresponding connector attached through the proximal hub 118. More specifically, the inflation tube lumen 110 is generally connected to an inflation connector 120, the infusion lumen 108 is connected to an infusion connector 122, the first drug lumen 112 is connected to a first drug connector 126, and the second drug lumen 114 is connected to a second drug connector 128. Each connector will include a luer connector or other conventional terminal element to removably connect to a suitable source of material, such as a perfusate, a drug, a protective medium or an inflation source, such as a syringe.

Each internal lumen within the catheter body 102 terminates at a port on the catheter body. In particular, the perfusion lumen 108 terminates in a transverse perfusion port 134. Inflation lumen 110 terminates in an inflation port 132, and first and

second drug lumens

112 and 114 terminate in a first drug port 138 and a second drug port 140, respectively. In this manner, it will be appreciated that fluids, drugs, inflation media, etc. may be delivered from each connector to their respective outlet ports in the elongate catheter body 102 by connection to an appropriate fluid or inflation source.

The catheter 100 also includes an inflatable occlusion element 144, typically an inflatable balloon, located on the outer surface of the catheter body 102 between the irrigation port 134 and the

drug delivery ports

138 and 140. As described below, there is an expandable occlusion element 144 between these ports that allows flow from each port to be selectively directed into either an antegrade or retrograde flow direction in the vein when the occlusion element 144 is expanded.

Referring now to fig. 82A, in some embodiments, the inflation connector 120 and the irrigation connector 122 may be fused or otherwise connected together to facilitate connection management during use. In particular, by bringing together the irrigation connector and the inflation connector, the user can easily identify the outer occlusion element 144 when it is desired to inflate and deliver a protective media through the irrigation connector 122.

As shown in fig. 82A, the inflatable occlusion element 144 is an inflatable balloon having a deflated configuration shown in solid lines. As shown in phantom, the balloon may be inflated to a generally cylindrical shape. As shown in fig. 84A-84C, the expandable occlusive element can have a variety of shapes, such as a spherical balloon 150 (fig. 84A), an expandable element having circumscribing ridges as shown at 152 in fig. 84B, and a tulip 154 as shown in fig. 84C. Such a tulip-shaped occlusion element 154 will typically have a concavity facing in the upstream direction, so that blood flow will cause the conical structure to expand and further seal the vein wall.

The placement and use of the catheter 100 is shown in fig. 85. Figure 85 shows venous and arterial blood vessels of a patient. Venous blood flows caudally from the right internal jugular vein 300 through the right brachiocephalic vein 301 into the superior vena cava 302 and into the right atrium 303 of the heart 310. Venous blood also returns to the right atrium 303 of the heart through the right brachiocephalic vein 303. Left 308 and right 301 brachiocephalic veins, assembled from right 304 and left 305 external jugular veins and left 306 and right 307 subclavian veins. Arterial flow is directed from the aorta 500 through the brachiocephalic artery 503, the left common carotid artery 506, and the left subclavian artery 507. From brachiocephalic artery 503, arterial blood flows to the right subclavian artery 508 and through the right common artery on the cranial side. The common carotid artery 509, which is divided into the right common internal carotid artery 510 and the right common external carotid artery 511. Arterial blood additionally flows from the left common carotid artery 506 to the left external carotid artery 512 and the left internal carotid artery 513.

As further shown in fig. 85, the catheter 100 is positioned as a typical central venous catheter with the distal end 104 positioned in the superior vena cava 302 at the entrance to the right atrium 303. The device hub 118 is sutured to the skin 801 for secure placement, with each of the four

connectors

120, 122, 126, and 128 being located externally for use by a medical team. The elongate catheter body 102 is introduced through the lumen of the right internal jugular vein 300 with the expandable occlusion element 144 in an unexpanded configuration. The expandable occlusion element 144 will typically be positioned over the interface with the right subclavian vein 307 and remain in an unexpanded configuration until delivery of a protective perfusion medium to the brain of the patient is desired, for example, during an in-home cardiac arrest (IHCA). Although in this configuration, the catheter 100 can be used to deliver drugs or other substances to the heart through the

drug lumens

112 and 114 and the

drug ports

138 and 140 in the same manner as a conventional central venous catheter.

When IHCA or other needs deliver a protective perfusion medium to the brain of a patient, the expandable occlusion element 144 expands to provide a complete occlusion of the right internal jugular vein 304. Partial or complete occlusion 307 of the right subclavian vein may also occur. As shown in this embodiment, the inflatable occlusion element 144 is an inflatable balloon and inflation is caused by delivery of saline or other inflation medium through the inflation connector 120 and inflation lumen 110, typically using a syringe. While reference has been made specifically to the intervention of the right internal jugular vein, it is understood that other portions of the vasculature may be accessed as well.

By occluding the right internal jugular vein 301 and optionally the right subclavian vein 307, antegrade venous flow through the right internal jugular vein 301 is prevented and retrograde flow of a protective medium (e.g., cooled crystalloid fluid) to the cerebral venous vasculature may occur.

Drug delivery to the heart may continue to occur through the second drug lumen 114 and port 140 or through the first drug lumen 112 and port 138, as appropriate. Countercurrent heat exchange between the right internal jugular vein 300 and the right internal

jugular vein

509, 510, 511 may then occur as this potentially cooled fluid is managed through the perfusion lumen 108 and the port 134. Despite the IHCA or other indications of use, including intentional cardiac arrest during cardiac surgery, arterial flow through the vessels will continue, none of these vessels will be occluded, and the patient will experience blood flow during CPR-related chest compressions. This arterial blood flow will further accommodate temperature exchange through this counter-current heat exchange, supplementing the temperature regulation achieved by direct exposure to potentially cooling fluids in the venous system.

Referring now to fig. 86, the system of the present invention generally includes a patient interface assembly 1000, an extracorporeal assembly 1200, and a fluid transfer assembly 1100 between the patient interface assembly and the extracorporeal assembly. The patient interface assembly 1000 generally includes an intravenous infusion catheter 1010 and an associated temperature sensor 1020. The extracorporeal component 1200 includes a crystal or other fluid 1210 to be contained within a specialized temperature conditioning vessel 1220, and a readout feature 1230 of the extracorporeal component. A temperature sensor. The fluid delivery assembly 1100 generally includes a temperature regulated tube, and the fluid 1210 to be administered will flow through the temperature regulated tube to the intravenous infusion catheter 1010, where it will be released into the vasculature of the patient and directed cranial. Temperature fluctuation data will be transmitted from the patient interface system 1000 to the extracorporeal system 1200.

Referring now to fig. 87A-87B, 88A-88D, and 89A-89B, an alternative dispensing system for an iv catheter in accordance with the principles of the present invention will be described. The flow of the dispensing system 1300 may be incorporated into an intravenous infusion catheter of the type previously disclosed. Flow rate distribution system 1300 utilizes a double-acting balloon configuration to simultaneously occlude venous flow and divert flow through the perfusion lumen from the distal or downstream side of the inflated balloon to the proximal or upstream side of the balloon.

The elongate catheter body 1302 includes an infusion lumen 1304, an inflation lumen 1306, a first drug lumen 1308, and a second drug lumen 1310. The

drug lumens

1308 and 1310 are only visible in the transverse cross-sectional views of fig. 88A-88D and 89A-89D, and are not visible in the axial cross-sectional views of fig. 87A-87B.

Irrigation lumen 1304 terminates at a distal port (not shown) for opening at the irrigation lumen (not occluded by a double-acting balloon or other mechanical occlusion device as described below). The perfusion lumen 1304 also has a second or cerebral perfusion port 1314 for delivering a perfusion medium (typically a protective perfusion medium) to the cerebral venous vasculature upon inflation of the double-acting balloon.

As shown in fig. 87A and fig. 88A-88D, the expandable occlusion element 1320, in the form of an expandable balloon, is in a collapsed configuration. When deflated, the proximal portion of balloon 1320 covers proximal irrigation port 1314 and occlusion port 1315.

However, as shown in fig. 87B and 89B, when the inflatable occlusion balloon 1320 is inflated by delivering an inflation medium through the inflation lumen 1306, the balloon expands and peels away to expose the proximal irrigation port 1314. In addition, the occlusion protrusions 1322 of the balloon expand radially inward through occlusion ports 1315 in the sidewall of the elongate catheter body 1302. Thus, flow of perfusion medium through the perfusion lumen 1304 is blocked by the expanded occlusion element 1320 and diverted through the uncovered perfusion port 1314 so that it can flow as previously described in a retrograde fashion into the patient's cerebral venous vasculature.

Referring now to fig. 90A and 90B, an intravenous infusion catheter 1400 with a tubular shunt is shown. Intravenous infusion catheter 1400 includes an elongated catheter body 1402 having an infusion lumen 1404 and an inflation lumen 1406. Catheters also typically include one or more additional drug delivery lumens, but such lumens are not visible in the axial cross-sectional views of fig. 90A and 90B.

Perfusion lumen 1404 includes a proximal or brain perfusion port 1414 and a distal or heart perfusion port 1418. Inflation lumen 1406 includes an inflation port 1416, which inflation port 1416 is positioned to inflate balloon-like inflatable occlusion element 1420 in a manner similar to the previous embodiment.

As shown in fig. 90A, the tubular shunt 1424 is in a proximally retracted position such that it covers the proximal or cerebral perfusion port 1414. That is, when the tubular shunt 1424 is proximally retracted, flow through the perfusion lumen 1404 cannot pass outwardly through the proximal or brain perfusion port 1414. Instead, flow through perfusion lumen 1404 will pass through the internal passage of tubular shunt 1424 so that it can flow out of distal or cardiac perfusion port 1418.

To divert the perfusion flow to the proximal or cerebral perfusion port 1414, as shown in fig. 90B, a tubular shunt 1424 is advanced distally to cover the distal or cardiac perfusion port 1418. The proximal or cerebral perfusion port 1414 is simultaneously uncovered so that flow can then pass radially outward through the proximal port. To ensure that flow from the proximal port 1414 flows in a retrograde fashion, the balloon-like expandable occlusion element 1420 as previously described is inflated by delivering inflation media through the inflation lumen 1406 and out through the inflation port 1416 to occlude the vein.

Referring now to fig. 21A and 21B, a perfusion balloon catheter 1500 is shown. The perfusion balloon catheter 1500 includes an elongate catheter body 1502 having a combined perfusion/inflation lumen 1504 and at least one additional drug or other fluid delivery lumen 1506. When used as a central access catheter, the irrigated version of the inflatable occlusion element balloon 1520 remains uninflated, as shown in fig. 91A. As shown in fig. 91A, a drug or other substance may be delivered through the drug delivery lumen 1506 and out through the drug infusion port 1508. As shown in fig. 91B, the drug may also be released through the second drug infusion port 1510.

When it is desired to deliver a perfusion medium (e.g., a brain protection medium) in a retrograde direction from the perfusion balloon catheter 1500, as shown in fig. 91B, a protective or other perfusion medium is delivered through the combined perfusion/inflation lumen 1504, thereby inflating the balloon occlusion element 1520. A plurality of drug release holes 1524 formed on the proximal or brain side of the inflated balloon open to release the inflated perfusion medium from the balloon in a retrograde direction (generally toward the patient's brain). If desired, the drug may be delivered through any available drug delivery lumen in the catheter.

The embodiments of the invention described above are intended to be exemplary only. Accordingly, the scope of the invention is intended to be limited only by the scope of the appended claims. While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Any element described herein as singular may be in plural (i.e., any element described as "a," "an," or "the" may be more than one). Any species element of a species element may have the characteristics or elements of any other species element of the genus. (for example, "central venous catheter" is used throughout this disclosure as an exemplary medical device, but may be any medical device or combination thereof. "heat exchanger" is used throughout this disclosure as an exemplary method of cooling matter, but may be any method for performing the above-described configurations, elements, or complete assemblies and methods of the invention and elements thereof, and variations of aspects of the invention may be combined with and modified from each other in any combination.

The present specification discloses embodiments including, but not limited to:

1. an intravenous infusion catheter assembly comprising:

an elongate catheter body having a proximal end and a distal end;

an expandable occlusion element disposed on the elongate catheter body;

a first infusion lumen extending from the proximal end of the catheter body to a proximal infusion port on the catheter body located proximal of the occlusion element between the occlusion element and the proximal end of the catheter body;

A second infusion lumen extending from the proximal end of the catheter body to a distal infusion port located on the catheter body distal to the occlusion element;

an aspiration lumen extending from a proximal end of the catheter body to at least one aspiration port on the catheter body positioned distal to the occlusion element; and

wherein the proximal infusion port and the distal infusion port are spaced relative to the occlusion element such that when the catheter is introduced into a patient's vasculature, the aspiration port is positioned in a superior vena cava or right atrium of the patient to draw blood flowing through the patient's vena cava, the distal infusion port is positioned in the superior vena cava or right atrium of the patient to direct a normothermic or hyperthermic fluid toward the patient's heart, and the proximal infusion port is positioned in an internal jugular vein of the patient to create retrograde flow of the cryogenic fluid in the patient's cerebral vasculature.

2. The iv catheter assembly of clause 1, further comprising an inflation lumen extending from the proximal end of the catheter body to the expandable occlusion element.

3. The iv infusion catheter assembly according to clause 1, further comprising a position marker positioned on the catheter body at or proximally adjacent to at least one of the aspiration port, the proximal infusion port, the distal infusion port.

4. The iv catheter assembly of clause 3, wherein the position marker is a radiopaque or ultrasound-opaque marker.

5. The iv catheter assembly of clause 1, further comprising a position marker on the distal end of the catheter body, the position marker comprising a radiopaque marker or an ultrasound-opaque marker.

6. The iv catheter assembly of clause 1, further comprising a heat exchange assembly fluidly connected with the aspiration lumen and at least one of the first infusion lumen or the second infusion lumen.

7. The iv catheter assembly of clause 6, further comprising a controller communicatively connected to the heat exchange assembly.

8. The iv catheter assembly of clause 7, wherein the heat exchange assembly further comprises a pump having an adjustable flow rate connected to the controller.

9. The iv catheter assembly of clause 7, wherein the controller is configured to adjust at least one of a flow rate of the pump or a temperature of the heat exchange assembly.

10. The iv catheter assembly of clause 7, wherein the controller is further configured to:

Receiving a brain temperature and a heart temperature; and

adjusting at least one of a flow rate of the pump or a temperature of the heat exchange assembly based on the brain temperature and the heart temperature.

11. The iv catheter assembly of clause 7, wherein the controller controls the heat exchange assembly to output cryogenic fluid to the first infusion lumen.

12. The iv catheter assembly of clause 7, wherein the controller controls the heat exchange assembly to output a normothermic or hyperthermic fluid to the second infusion lumen.

13. The iv catheter assembly of clause 6, wherein the heat exchange assembly and the controller are integrated into a housing.

14. The iv catheter assembly of clause 1, further comprising a temperature sensor positioned on or in the catheter body distal to the occlusion element or in a suction tube.

15. The iv catheter assembly of clause 1, further comprising a guidewire extending from the proximal end of the catheter body to the distal end of the catheter body.

16. The iv infusion catheter assembly of clause 1, further comprising a second expandable element disposed on the elongate catheter body and positioned on the catheter body distal to the occlusion element between the occlusion element and the suction port such that the suction port is not occluded by the patient's vein wall.

17. The iv catheter assembly of clause 16, wherein the second expandable element is non-occlusive.

18. The iv catheter assembly of clause 1, wherein the normothermic or hyperthermic fluid comprises blood at a temperature between 36 degrees celsius and 42 degrees celsius.

19. The iv catheter assembly according to clause 1, wherein the cryogenic fluid comprises blood at a temperature between 0 degrees celsius and 36 degrees celsius.

20. The intravenous infusion catheter assembly of clause 1, wherein the first infusion lumen comprises an insulating layer.

21. The iv catheter assembly of clause 1, wherein the normothermic or hyperthermic fluid comprises aspirated blood.

22. The iv catheter assembly according to clause 1, wherein the cryogenic fluid comprises cooled aspirated blood.

23. The iv catheter assembly of clause 1, wherein at least one of the pressure lumen, the first infusion lumen, the second infusion lumen, or the aspiration lumen extending through the catheter body comprises a reinforced coil or a hypotube.

24. The iv catheter assembly of clause 1, further comprising a pressure lumen extending from the proximal end of the catheter body to a port located proximal of the expandable occlusion element.

25. The iv catheter assembly of clause 1, further comprising a mounting fixture.

26. The iv catheter assembly of clause 1, further comprising a tapered tip positioned at the distal end of the catheter body.

27. The iv catheter assembly of clause 26, wherein the tapered tip is constructed of a lower durometer material than the catheter body.

28. The iv infusion catheter assembly of clause 1, further comprising a second aspiration port fluidly connected to an aspiration lumen and positioned on the catheter body distal to the occlusion element between the occlusion element and the distal infusion port.

29. The iv infusion catheter assembly according to clause 1, further comprising a second aspiration port fluidly connected to the aspiration lumen and positioned on the catheter body distal to the distal infusion port.

30. The iv catheter assembly of clause 1, wherein the catheter body is introduced into the vasculature of the patient in a first direction to deliver a flow of fluid through the catheter and is directed in a direction opposite the first direction.

31. A method for treating a patient, the method comprising:

creating an occlusion in an internal jugular vein of the patient with an expandable occlusion element disposed on a catheter having a proximal end and a distal end;

drawing blood from the superior vena cava of the patient through a suction port into a suction lumen extending through the catheter;

delivering cryogenic fluid from a first heat exchange assembly through a first infusion lumen extending from the proximal end of the catheter body to a proximal infusion port and out of the proximal infusion port to create retrograde flow in the patient's cerebral vasculature; and

delivering a normothermic or hyperthermic fluid through a second infusion lumen extending from the proximal end of the catheter body to a distal infusion port and out of the distal infusion port to direct the normothermic or hyperthermic fluid toward the patient's heart.

32. The method of clause 31, wherein the proximal infusion port on the proximal end of the catheter is positioned in the internal jugular vein of the patient.

33. The method of clause 31, wherein the distal infusion port on the distal end of the catheter is positioned in the right atrium or superior vena cava of the patient at or near the patient's atrial junction.

34. The method of clause 31, wherein the aspiration port is positioned on the distal end of the catheter and proximal to the distal infusion port, and is positioned in the right atrium or superior vena cava of the patient.

35. The method of clause 31, wherein delivering the normal or high temperature fluid begins with a second heat exchange assembly.

36. The method of clause 35, further comprising:

receiving a cardiac temperature based on measurements of a temperature sensor positioned distal to the occlusion element on or in the catheter; and

adjusting the second heat exchange assembly based on the heart temperature to output a normal or high temperature fluid at a temperature between 36 degrees Celsius and 42 degrees Celsius.

37. The method of clause 31, wherein the first heat exchange assembly comprises a pump having an adjustable flow rate.

38. The method of clause 37, further comprising:

receiving a heart temperature based on measurements of a temperature sensor positioned distal to the occlusion element on or in the catheter; and

if the heart temperature is below 32 degrees Celsius, the flow rate of the pump is decreased.

39. The method of clause 31, further comprising inflating a non-occlusive expandable element disposed on the catheter between the expandable occlusion and the aspiration port such that the aspiration port is not occluded by a vein wall of the patient.

40. The method of clause 31, wherein the normothermic or hyperthermic fluid comprises aspirated blood.

41. The method of clause 31, wherein the cryogenic fluid comprises cooled pumped blood.

42. The method of clause 31, wherein the cryogenic fluid comprises blood at a temperature between 0 and 36 degrees celsius.

43. The method of clause 31, wherein the catheter further comprises a position marker positioned on the catheter body at or proximally adjacent to at least one of the aspiration port, the proximal infusion port, the distal infusion port.

44. The method of clause 43, wherein the position marker is a radiopaque or ultrasound-opaque marker.

45. The method of clause 31, wherein the catheter further comprises a position marker on the distal end of the catheter body, the position marker comprising a radiopaque marker or an ultrasound-opaque marker.

46. The method of clause 31, further comprising warming the patient's body with a warming blanket.

47. A method for treating a patient, the method comprising:

receiving a brain temperature based on a measurement of a first temperature sensor;

receiving a heart temperature based on measurements of a second temperature sensor located on or in the catheter distal to the occlusion element or in an aspiration tube;

determining whether the heart temperature is below a second predetermined temperature and if the heart temperature is below the second predetermined temperature, communicating a command to a second heat exchange assembly to increase a second flow rate;

determining whether the brain temperature is above a first predetermined temperature if the heart temperature is not below the second predetermined temperature; and

in response to determining that the brain temperature is above a first predetermined temperature, a command is transmitted to the first heat exchange assembly to increase the first flow rate.

48. The method of clause 47, wherein the second predetermined temperature is 36 degrees celsius.

49. The method of clause 47, wherein the first predetermined temperature is between 32 and 33 degrees celsius.

50. The method of clause 47, wherein the first temperature sensor comprises at least one of a nasopharyngeal temperature sensor, an tympanic temperature sensor, or an essentially internal temperature sensor.

51. The method of clause 47, further comprising receiving a conduit pressure measurement and transmitting a command to the first heat exchange assembly to decrease the first flow rate when the pressure measurement is greater than 30mmHg for a predetermined amount of time.

52. The method of clause 47, further comprising receiving a conduit pressure measurement and transmitting a command to the second heat exchange assembly to decrease the second flow rate when the pressure measurement is greater than 30mmHg for a predetermined amount of time.

53. The method of clause 47, further comprising receiving a pressure measurement from at least one of the first heat exchange assembly or the second heat exchange assembly, and transmitting a command to the respective at least one heat exchange assembly to decrease the corresponding flow rate when the pressure measurement is greater than 400 mmHg.

54. The method of clause 47, further comprising receiving a pressure measurement from at least one of the first heat exchange assembly or the second heat exchange assembly, and transmitting a command to the respective heat exchange assembly to decrease the corresponding flow rate when the pressure measurement is less than-300 mmHg.

55. The method of clause 47, further comprising comparing the first flow rate to a first predetermined threshold and transmitting a command to the first heat exchange assembly to decrease the first flow rate when the first flow rate exceeds the first predetermined threshold.

56. The method of clause 47, further comprising comparing the second flow rate to a second predetermined threshold and transmitting a command to the second heat exchange assembly to decrease the second flow rate when the second flow rate exceeds the second predetermined threshold.

57. The method of clause 47, wherein the catheter draws blood from the superior vena cava of the patient through a suction port into a suction lumen extending through the catheter and delivers the blood to the first and second heat exchange assemblies.

58. The method of clause 47, wherein the first heat exchange assembly delivers cryogenic fluid through a first infusion lumen extending from the proximal end of the catheter body to a proximal infusion port and out the proximal infusion port to create retrograde flow in the patient's cerebral vasculature.

59. The method of clause 47, wherein the second heat exchange assembly delivers a normothermic or hyperthermic fluid through a second infusion lumen extending from the proximal end of the catheter body to a distal infusion port and out of the distal infusion port to direct the normothermic or hyperthermic fluid toward the patient's heart.

60. The method of clause 47, further comprising:

receiving a first flow rate from a first heat exchange assembly, the first flow rate indicative of a flow rate from the catheter into the patient's cerebral vasculature; and

receiving a second flow rate from a second heat exchange assembly, the second flow rate indicative of a flow rate from the catheter directed to the patient's heart.

61. The method of clause 47, further comprising transmitting commands to the second heat exchange assembly to increase the second flow rate immediately prior to transmitting commands to the first heat exchange assembly to increase the first flow rate.

62. A method for treating a patient, the method comprising:

creating an occlusion in an internal jugular vein of the patient with an expandable occlusion element disposed on a catheter having a proximal end and a distal end and a valve positioned in the catheter and positioned distally adjacent to the expandable occlusion element;

delivering cryogenic fluid through the proximal end by:

cooling the infused fluid with a cooled wall positioned proximal to the expandable occlusion element; and is

Generating a proximal fluid flow with a proximal impeller positioned proximal of the expandable occlusion element in the catheter; and

delivering a normal or high temperature fluid through the distal end by:

warming the infused fluid with a heated wall positioned distal to the expandable occlusion element; and is

Generating a distal fluid flow with a distal impeller positioned in the catheter distal to the expandable occlusion element.

The claims (modification according to treaty clause 19)

1. An intravenous infusion catheter assembly comprising:

an elongate catheter body having a proximal end and a distal end;

an expandable occlusion element disposed on the elongate catheter body;

2. The iv catheter assembly of claim 1, further comprising an inflation lumen extending from the proximal end of the catheter body to the expandable occlusion element.

3. The iv catheter assembly of claim 1, further comprising a heat exchange assembly fluidly connected with the aspiration lumen and at least one of the first infusion lumen or the second infusion lumen.

4. The iv catheter assembly of claim 3, further comprising a controller communicatively connected to the heat exchange assembly.

5. The iv catheter assembly of claim 4, wherein the controller is further configured to:

receiving a brain temperature and a heart temperature; and

6. The iv catheter assembly of any of claims 1-5, further comprising a temperature sensor positioned on or in the catheter body distal to the occlusion element or in an aspiration tube.

7. The iv infusion catheter assembly of any of claims 1-5, further comprising a second expandable element disposed on the elongate catheter body and positioned on the catheter body distal of the occlusion element between the occlusion element and the suction port such that the suction port is not occluded by the patient's vein wall.

8. The iv catheter assembly of any of claims 1-5, wherein the normothermic or hyperthermic fluid comprises blood at a temperature between 36 degrees Celsius and 42 degrees Celsius.

9. A method for treating a patient, the method comprising:

drawing blood from the superior vena cava of the patient through an aspiration port into an aspiration lumen extending through the catheter;

10. The method of claim 9, wherein a proximal infusion port on the proximal end of the catheter is positioned in the patient's internal jugular vein.

11. The method of any of claims 9-10, wherein a distal infusion port on a distal end of the catheter is positioned in the right atrium or superior vena cava of the patient at or near an interatrial junction of the patient.

12. The method of any of claims 9-10, wherein the aspiration port is positioned on a distal end of the catheter and proximal to the distal infusion port, and in a right atrium or superior vena cava of the patient.

13. The method of any one of claims 9 to 10, wherein delivering the normal or high temperature fluid begins at a second heat exchange assembly.

14. The method of claim 13, further comprising:

15. A therapeutic system, comprising:

means for performing the steps of the method according to any one of claims 9 to 10.

Claims

1. An intravenous infusion catheter assembly comprising:

an elongate catheter body having a proximal end and a distal end;

an expandable occlusion element disposed on the elongate catheter body;

3. The iv catheter assembly of any of claims 1-2, further comprising a heat exchange assembly fluidly connected with the aspiration lumen and at least one of the first infusion lumen or the second infusion lumen.

receiving a brain temperature and a heart temperature; and

7. The iv infusion catheter assembly of any of claims 1-6, further comprising a second expandable element disposed on the elongate catheter body and positioned on the catheter body distal of the occlusion element between the occlusion element and the suction port such that the suction port is not occluded by the patient's vein wall.

8. The iv catheter assembly of any of claims 1-7, wherein the normothermic or hyperthermic fluid comprises blood at a temperature between 36 degrees celsius and 42 degrees celsius.

9. A method for treating a patient, the method comprising:

12. The method of any of claims 9-11, wherein the aspiration port is positioned on a distal end of the catheter and proximal to the distal infusion port, and in a right atrium or superior vena cava of the patient.

13. The method of any one of claims 9 to 12, wherein delivering the normal or high temperature fluid begins with a second heat exchange assembly.

14. The method of claim 13, further comprising:

15. A therapeutic system, comprising:

means for performing the steps of the method according to any one of claims 9 to 14.