Methods and systems for manipulating body characteristics using a fluid exchange catheter system

Abstract

A method is described for selectively changing the temperature of a cavity from a reference temperature to a target temperature different from the reference temperature. The method includes turning on an infusion mechanism to infuse fluid into the cavity through a first fluid pathway and an infusion lumen in a catheter component for an infusion time. The fluid is brought to a target fluid temperature before reaching the cavity. The method also includes periodically or continuously removing at least a portion of the fluid through a second fluid pathway, monitoring the temperature of the cavity, and maintaining the target temperature for a predetermined time.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application Ser. No. 63 / 382,396, filed November 4, 2022, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to methods and systems for manipulating body characteristics or biomarkers, such as temperature and pH, using a fluid exchange catheter system. [Background technology]

[0003] Therapeutic hypothermia (TH), which prevents or reduces irreversible neuronal necrosis and ischemic brain damage, has proven effective in both animal and clinical studies to prevent ischemia-reperfusion injury in postcardiac arrest syndrome and neonatal encephalopathy. However, lowering whole-body temperature below 34°C can lead to serious systemic complications, including cardiac, hematologic, immune, and metabolic side effects. Although the brain accounts for only 2% of total body weight, it consumes 20% of the body's energy at rest and requires a continuous supply of glucose and oxygen to maintain its function and structural integrity. Temperature-controlled selective brain cooling (SBC) may be more beneficial in cerebral ischemia than in generalized ischemia. Various SBC methods have been introduced to selectively cool the brain while minimizing systemic TH-related complications. However, technical drawbacks of conventional SBC, such as insufficient cooling output, relatively expensive cooling agents, and / or irritating effects on the skin and mucous membrane interfaces, limit its application in various clinical settings.

[0004] Acute brain injury can lead to distal organ damage even in the absence of systemic disease or inflammation. This type of injury affects not only the brain but the entire body, necessitating a mind-body approach to treatment. Systemic TH can help mitigate this type of brain injury but can also cause systemic complications that affect biological survival processes. Induction and maintenance of systemic hypothermia in warm-blooded mammals can cause physiological side effects, some of which can lead to morbidity and death. TH side effects can be categorized into cardiac, immune, and metabolic complications. Common side effects of TH include hyperglycemia, shivering, bradycardia, electrolyte abnormalities, acute kidney injury, pneumonia, and hypercoagulability or hypocoagulability syndromes. Physiological adverse events caused by systemic TH require specialized intensive care resources, sedatives, muscle relaxants, mechanical ventilation, and combinations thereof. Therefore, these physiological complications must be carefully considered and closely monitored in the intensive care unit, and patients undergoing TH should be admitted to the intensive care unit. This requirement may be another obstacle to the application of systemic TH. In recent years, drug-induced hypothermia has emerged as an alternative option to avoid the complications of systemic TH. It has been reported that drugs targeting thermoreceptors may be an effective strategy for treating stroke in conscious subjects, even when initiated long after reperfusion. Combination therapy with pharmacological and physical TH may effectively reduce side effects by reducing the drug dose and the time required to reach the therapeutic goal.

[0005] SBC can be performed using three approaches to reach target temperatures in patients with acute brain injury. The three main mechanisms of SBC are: (1) direct superficial cooling of the scalp, (2) intravascular cooling, which allows heat exchange between the internal carotid artery and intracranial venous drainage, and (3) intranasal cooling, which allows rapid heat exchange in the upper airway.

[0006] Besides temperature, other body parameters, traits, and biomarkers can be manipulated to similarly provide important physiological benefits.

[0007] The following references provide further background and are expressly incorporated herein by reference: ·Hong et al., “Selective Brain Cooling: A New Horizon of Neuroprotection,” Front.Neurol., 20 June 2022, Sec.Endovascular and Interventional Neurology, vol. 13 (2022). https: / / doi.org / 10.3389 / fneur.2022.873165 ·Mattingly et al., “The Complex Relationship Between Cooling Parameters and Neuroprotection in a Model of Selective Hypothermia,” Front.Neurol., 25 April 2022, Sec. Endovascular and Interventional Neurology, vol. 13 (2022). https: / / doi.org / 10.3389 / fneur.2022.874701 ·Horn et al., “Non-invasive Brain Temperature Measurement in Acute Ischemic Stroke,” Front.Neurol., 05 August 2022, Sec. Endovascular and Interventional Neurology, vol. 13 (2022). https: / / doi.org / 10.3389 / fneur.2022.889214 ·Wang et al., “Updates on Selective Brain Hypothermia:Study From Bench Work to Clinical Trials,” Front.Neurol., 06 May 2022, Sec. Endovascular and Interventional Neurology, vol. 13 (2022). https: / / doi.org / 10.3389 / fneur.2022.899547 ·Magnoni et al., “A Novel Cooling Device for Targeted Brain Temperature Control and Therapeutic Hypothermia:Feasibility Study in an Animal Model,” Neurocrit Care, December 2016, vol. 25, issue 3, pages 464-472, doi: 10.1007 / s12028-016-0257-7, PMID: 26927280, PMCID: PMC5138276. ·Harris et al., “Systematic review of head cooling in adults after traumatic brain injury and stroke,” Health Technology Assessment, November 2012, vol. 16, issue 45. https: / / doi.org / 10.3310 / hta16450 Summary of the Invention

[0008] To meet at least the aforementioned needs, the present disclosure provides a method for selectively varying the temperature of a body cavity from a reference temperature to a target temperature different from the reference temperature. The method includes turning on an infusion mechanism to infuse a fluid into the cavity via a first fluid pathway and an infusion lumen in a catheter component for an infusion time. The fluid is brought to a target fluid temperature before reaching the cavity. The method also includes periodically or continuously removing at least a portion of the fluid via a second fluid pathway, monitoring the temperature of the cavity, and maintaining the target temperature for a predetermined time.

[0009] In another aspect, the present disclosure provides a system for altering the temperature of a cavity, the system comprising a fluid set and a catheter component adapted for insertion into the cavity, the system further comprising a fluid source containing a fluid, an infusion mechanism comprising a pump adapted to deliver the fluid from the fluid source to the catheter component, a drainage line adapted to remove at least a portion of the fluid, one or more temperature sensors adapted to measure a temperature within the cavity, and a heat exchange unit adapted to heat or cool the fluid before it reaches the cavity.

[0010] In another aspect, the present disclosure provides a method for manipulating the state of one or more physiological biomarkers in a target region of a cavity using a fluid exchange catheter system. The fluid exchange catheter system includes multiple fluid paths. A first fluid path is defined by a proximal end, a distal end, and a lumen wall extending between the proximal and distal ends. A second fluid path is defined by a proximal end, a distal end, and a lumen wall extending between the proximal and distal ends. The system also includes an aspiration mechanism operably connected to the proximal end of the first lumen and an infusion mechanism operably connected to the proximal end of the second lumen. The method includes the steps of: (a) turning on the injection mechanism with the suction mechanism off to inject an injection fluid into the target area of ​​the cavity of the patient through the first fluid pathway for an injection time or injection volume; (b) turning off the injection mechanism to stop the injection; (c) turning on the suction mechanism with the injection mechanism off to aspirate fluid from the target area of ​​the patient through the second fluid pathway for an aspiration time or aspiration volume; (d) turning off the aspiration mechanism to stop aspiration; and (e) repeating steps (a) through (d). Steps (a) through (d) do not need to be performed in any particular order.

[0011] This disclosure is also disclosed in the following clauses:

[0012] Clause 1 1. A method for selectively changing the temperature of a cavity from a reference temperature to a target temperature different from the reference temperature, comprising: (a) turning on an infusion mechanism to infuse fluid into the cavity through a first fluid pathway and an infusion lumen in a catheter component for an infusion time, the fluid being brought to a target fluid temperature before reaching the cavity; and (b) periodically or continuously removing at least a portion of the fluid through a second fluid pathway. (c) monitoring the temperature of the cavity; and (d) maintaining the target temperature for a predetermined period of time.

[0013] Clause 2 10. The method of claim 1, wherein the cavity is the brain.

[0014] Clause 3 3. The method of claim 1 or 2, wherein the fluid is a refrigerated fluid and is brought to the target fluid temperature using a cooling unit selected from the group consisting of one or more ice packs, one or more ice baths, a freezer, and a refrigerator.

[0015] Clause 4 4. The method according to any one of clauses 1 to 3, wherein the target temperature is between 30°C and 35°C.

[0016] Clause 5 5. The method according to any one of clauses 1 to 4, wherein the target temperature is 4°C to 8°C lower than the reference temperature.

[0017] Clause 6 6. The method of any one of clauses 1 to 5, wherein the target fluid temperature is between 15°C and 20°C.

[0018] Clause 7 7. The method according to any one of clauses 1 to 6, wherein the predetermined time is 24 hours to 72 hours.

[0019] Article 8 8. The method of any of clauses 1-7, wherein the second fluid pathway is a drainage line placed in the spinal column.

[0020] Article 9 9. The method of clause 8, wherein the drainage line drains the fluid to a drainage receptacle.

[0021] Article 10 10. The method of any of clauses 1-9, wherein the second fluid pathway is a suction lumen in the catheter component.

[0022] Article 11 The catheter component is a dual lumen catheter or a dual single lumen catheter. 11. The method according to any one of clauses 1 to 10.

[0023] Article 12 12. The method of any of clauses 1-11, further comprising gradually returning the cavity to a temperature within 1-2°C of the reference temperature.

[0024] Article 13 13. The method of claim 12, wherein gradually returning the cavity to a temperature within 1-2°C of the reference temperature comprises increasing the temperature of the cavity by 0.05°C to 0.2°C per hour.

[0025] Article 14 14. The method of any of clauses 1 to 13, wherein the fluid has a composition substantially similar to that of cerebrospinal fluid.

[0026] Article 15 15. The method of any of clauses 1 to 14, wherein the fluid is lactated Ringer's solution or saline.

[0027] Article 16 16. The method of any of clauses 1-15, wherein the fluid comprises one or more anti-inflammatory agents.

[0028] Article 17 17. The method of any of clauses 1-16, further comprising providing a visual or audio indicator if the monitored temperature differs from the target temperature by a threshold value.

[0029] Article 18 17. The method of any of clauses 1-16, further comprising providing a visual or audio indicator if the monitored temperature differs from the target temperature by a threshold value.

[0030] Article 19 18. The method according to any one of clauses 1 to 17, wherein said method is carried out on a patient suffering from neuroinflammation.

[0031] Article 20 1. A system for altering the temperature of a cavity, the system comprising: a catheter system comprising a fluid set and a catheter part adapted for insertion into the cavity; a fluid source containing a fluid; an injection mechanism comprising a pump adapted to deliver the fluid from the fluid source to the catheter part; a drainage line adapted to remove at least a portion of the fluid; one or more temperature sensors adapted to measure the temperature within the cavity; and a heat exchange unit adapted to heat or cool the fluid before it reaches the cavity.

[0032] Article 21 21. The system of clause 20, wherein the drainage line is a spinal drainage line adapted for insertion into the patient's spine.

[0033] Article 22 22. The system of clause 20 or 21, wherein the heat exchange unit is a cooling unit selected from the group consisting of one or more ice packs, one or more ice bath containers, a freezer, and a refrigerator.

[0034] Article 23 23. The system of any of clauses 20-22, wherein the catheter component is a dual lumen catheter or a dual single lumen catheter.

[0035] Article 24 1. A method of manipulating a state of one or more physiological biomarkers within a target region of a cavity using a fluid exchange catheter system, the fluid exchange catheter system comprising a catheter component having a plurality of fluid pathways, an aspiration mechanism, and an infusion mechanism, wherein a first fluid pathway is formed by a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end, and a second fluid pathway is formed by a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end, the aspiration mechanism operably connected to the proximal end of the first lumen, and the infusion mechanism operably connected to the proximal end of the second lumen, the method comprising: (a) (b) turning on the injection mechanism and injecting injection fluid into the target area of ​​the cavity of the patient through the first fluid path for an injection time or injection volume while the suction mechanism is off; (b) turning off the injection mechanism and stopping the injection; (c) turning on the suction mechanism and aspirating fluid from the target area of ​​the patient through the second fluid path for an aspiration time or aspiration volume while the injection mechanism is off; (d) turning off the aspiration mechanism and stopping the aspiration; and (e) repeating steps (a) through (d), wherein steps (a) through (d) do not need to be performed in any particular order.

[0036] Article 25 25. The method of clause 24, wherein steps (c) and (d) precede steps (a) and (b), such that the aspiration precedes the injection.

[0037] Article 26 25. The method of clause 24, wherein steps (a) and (b) precede steps (c) and (d), such that the injecting precedes the aspiration.

[0038] Article 27 27. The method of any one of clauses 24 to 26, wherein the catheter component is a dual lumen catheter or a duplex single catheter.

[0039] Article 28 28. The method of any of clauses 24-27, wherein said physiological biomarker(s) comprises temperature, intracranial pressure, pH, oxygen, sodium, glucose, creatinine, carbon dioxide, chloride, protein, or similar attributes in blood or cerebrospinal fluid chemistry, and combinations thereof.

[0040] Article 29 29. The method of any of clauses 24-28, wherein the infusion fluid is selected from the group consisting of saline, lactated Ringer's solution, or other physician-prescribed fluids.

[0041] Article 30 30. The method of any of clauses 24 to 29, further comprising the step of injecting a drug into the cavity via one or more of the fluid pathways.

[0042] Article 31 31. The method of clause 30, wherein the infusion fluid comprises the drug.

[0043] Article 32 31. The method of clause 30, wherein the drug is selected from the group consisting of a thrombolytic drug, an antibiotic, or other physician-prescribed infusion drug, or a combination thereof.

[0044] Article 33 33. The method of any of clauses 24 to 32, wherein the cavity is the brain.

[0045] Article 34 34. The method of clause 33, wherein the injection fluid is injected into the ventricular system in the brain.

[0046] Article 35 35. The method of any of clauses 24 to 34, wherein steps (a) to (d) are repeated until target levels of temperature, pH, and / or other relevant biomarkers are achieved in the target region of the cavity.

[0047] Article 36 36. The method of any one of clauses 24 to 35, wherein the patient is suffering from neuroinflammation.

[0048] Article 37 37. The method of any of clauses 24 to 36, wherein the patient is at risk of neuronal necrosis and / or ischemic brain damage.

[0049] Article 38 38. The method of any of clauses 24 to 37, wherein steps (a) to (d) are repeated until inflammation is reduced by a clinically effective amount.

[0050] These and other features and characteristics of the present disclosure will become more apparent from a consideration of the following description and appended claims, taken in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0051] [Figure 1] FIG. 1 is a perspective view of a fluid exchange system according to an embodiment of the present disclosure. [Figure 2] 2 is a left perspective view of the control unit of the fluid exchange system of FIG. 1. FIG. [Figure 3] 3 is a right perspective view of the control unit of FIG. 2. FIG. [Figure 4] FIG. 4 is a rear view of the control unit of FIG. [Figure 5] 5 is a front view of the tubeset fitting of the fluid exchange system of FIG. 1. FIG. [Figure 6] FIG. 6 is a schematic diagram of the operating system of the fluid exchange system of FIG. [Figure 7] FIG. 7 is a perspective view of a catheter according to one embodiment of the present disclosure. [Figure 8]FIG. 8 is a cross-sectional view of the catheter of FIG. [Figure 9] FIG. 9 is a cross-sectional view of the distal tip of the catheter of FIG. 7 taken along line AA. [Figure 10] FIG. 10 is a perspective view of a distal tip of a catheter according to an embodiment of the present disclosure. [Figure 11] FIG. 11 is a perspective view of a configuration for using a spinal drainage line according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0052] For purposes of the following description, spatial orientation terms refer to the embodiments as oriented in the drawings. However, it should be understood that various embodiments of the present disclosure may assume alternative variations and step sequences, unless expressly specified to the contrary. It should also be understood that the specific devices and processes illustrated in the accompanying drawings and described in the following specification are merely exemplary. Hence, specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered limiting.

[0053] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0054] Unless otherwise indicated, all ranges or ratios disclosed herein should be understood to encompass any and all subranges or subratios subsumed therein. For example, a range or ratio of "1 to 10" includes, but is not limited to, all subranges between (and including) the minimum value of "1" and the maximum value of "10," i.e., all subranges or subratios beginning with a minimum value of "1" or greater and ending with a maximum value of "10" or less, such as "1 to 6.1," "3.5 to 7.8," "5.5 to 10," etc.

[0055] All documents referred to herein, including but not limited to issued patents and patent applications, are to be deemed "incorporated by reference" unless otherwise specified.

[0056] Methods and systems are provided for manipulating one or more physiological characteristics or biomarkers of a cavity in a body part using a fluid exchange catheter system. Non-limiting examples of physiological biomarkers that can be manipulated using a fluid exchange catheter system include temperature, pressure (e.g., intracranial pressure), pH, oxygen, sodium, glucose, creatinine, carbon dioxide, chloride, protein, or similar attributes in blood or cerebrospinal fluid chemistry, and combinations thereof.

[0057] The methods and systems disclosed herein can use a fluid exchange catheter system to deliver and remove (e.g., drain) one or more fluids from a target region in order to manipulate one or more properties. For example, a fluid exchange catheter system can deliver a cooling fluid to the central nervous system ("CNS") or a portion thereof (e.g., the brain or spinal column / spinal cord) to alter (e.g., lower or raise) its temperature. The fluid exchange catheter system can also remove fluids, such as a patient's spent cooling fluid and / or cerebrospinal fluid ("CSF"), from the CNS, e.g., by drainage. Removal can ensure that additional fluid can be added without increasing pressure. The methods and systems disclosed herein can enable targeted, selective manipulation of bodily properties. For example, the methods and systems disclosed herein can provide targeted cooling of the brain and / or CNS without other parts of the body (e.g., other organs such as the heart or lungs) receiving the same cooling effect or being cooled to the same extent. Lowering the temperature of the brain and other body parts has various benefits, such as reducing edema (tissue stretching to maintain its intact structure) and reducing tissue metabolism and inflammation that can be caused by trauma (mechanical disruption) or ischemia (lack of oxygen). At the same time, selective, or targeted, cooling of targeted areas offers an additional benefit in that it avoids systemic hypothermia and the problems that can result from cooling the heart, lungs, arteries, and other body parts.

[0058] Referring to FIG. 1 , a fluid exchange system 2 according to one non-limiting embodiment of the present disclosure is shown and described. In one aspect, the system 2 includes a control unit 4 that connects to an intravenous ("IV") pole 6 or other support structure, a tubing set attachment 8, a fluid source 10, and a drainage receptacle 12. The control unit 4, drainage receptacle 12, and fluid source 10 may be connected to the IV pole 6 using any suitable connection means for securing the control unit 4 and drainage receptacle 12 to the IV pole 6. The fluid source 10 and drainage receptacle 12 are fluidly connected to the tubing set attachment 8. In one aspect, the fluid source 10 is an infusion bag. In one aspect, the drainage receptacle 12 is a suction bag. The fluid source 10 may be located above the tubing set attachment 8 and directs fluid to the tubing set attachment 8. Drainage receptacle 12 may be located below tubeset fitting 8 and receives fluids drained from the patient through tubeset fitting 8. System 2 also includes tubing set 36 and refrigeration unit 88, which are described below.

[0059] 2-6, the control unit 4 of system 2 is shown and described in more detail. Control unit 4 may be a computer-based management system. The management system may utilize, for example, software and / or firmware to control pumps and sensors and enable proper delivery of fluids. The software and / or firmware may include algorithms in the form of programming instructions stored on a non-transitory machine-readable medium associated with system 2. The programming instructions may be executed by a processor associated with control unit 4 to enable control unit 4 to perform the various tasks and methods described herein.

[0060] The control unit 4 may include a pump 66 configured to direct fluid through the tubeset fitting 8. The pump 66 may be configured to direct fluid from the fluid source 10 to the patient through the tubeset fitting 8. The pump 66 may also be configured to generate or create a negative pressure within the tubeset fitting 8 to drain fluid from the patient through the tubeset fitting 8 and into the drainage receptacle 12. Pumps suitable for use in the present disclosure are generally known. In one embodiment, the pump 66 is a peristaltic pump. The control unit 4 may also include a pinch valve for controlling the flow of fluid through the tubeset fitting 8. The pump 66 and the pinch valve may be retained within the housing 14 of the control unit 4. The control unit 4 may also include a connection port 16 for receiving the tubeset fitting 8.

[0061] The control unit 4 may further include a graphical user interface ("GUT") 18 for displaying control options, alarm indications, and system parameters for the system 2 to a patient or medical personnel. In one embodiment, the GUT 18 includes an LCD touchscreen display to allow a medical personnel to operate the control unit 4. The control unit 4 also includes a central processing unit ("CPU") configured to operate the pump 66 housed within the control unit 4. The CPU may also communicate with sensors provided in the system 2 to measure and record system operating parameters and alarm indications for the control unit 4.

[0062] System 2 may also include flow sensors, algorithms, and associated methods for controlling the function of the pump motor to achieve precise control of infusion, both in volume, rate, duration, post-infusion pause period, and pressure measurement interval, to deliver fluids, medicinal agents, alter tissue effects and responses, achieve a desired therapeutic effect, meet safety requirements, manage clog removal of catheter 44 and tubing set 36, and achieve desired flow characteristics. The flow sensor may be, for example, a MEMS-based flow sensor or an impeller-driven flow meter.

[0063] Continuing to refer to FIG. 3 , the control unit 4 may also include a drainage receptacle hanger 32 configured to hold the drainage receptacle 12. In one embodiment, the drainage receptacle 12 is a suction bag. The drainage receptacle hanger 32 may include a graduated measuring band 34. The graduated measuring band 34 has one end connected to the control unit 4 and an opposite end connected to the drainage receptacle 12. The graduated measuring band 34 allows the drainage receptacle 12 to be vertically adjusted relative to the control unit 4. The graduated measuring band 34 may also indicate the vertical distance between the control unit 4 and the drainage receptacle 12. Once the drainage receptacle 12 is vertically adjusted relative to the control unit 4, a medical professional can measure the vertical distance between the drainage receptacle 12 and the control unit 4, or in other embodiments, the vertical distance between the drainage receptacle 12 and a patient's head positioned adjacent to the system 2. In one embodiment, the graduated measuring band 34 includes a measurement (e.g., inches, centimeters, etc.) provided thereon. The measurement determines the vertical distance between the drainage receptacle 12 and the control unit 4.

[0064] Referring to FIG. 6 , the operating system configuration of system 2 is shown and described according to one non-limiting embodiment. Control unit 4 can communicate with various data sources, including the keypad and / or touchscreen 46 of GUI 18, pressure sensor calibration knob 42, real-time clock calendar 48, flash memory 50, USB host 52, and service port 54. In one embodiment, control unit 4 also communicates with at least one pressure sensor 56 configured to record measurements of fluid pressure in system 2. In one embodiment, pressure sensor 56 can be located on at least one of control unit 4, tubeset attachment 8, and catheter 44. In another embodiment, one or more temperature sensors 76, 78 can be located on at least one of tubeset attachment 8, tubeset 36, and catheter 44. In another embodiment, control unit 4 also communicates with safety module 58. Control unit 4 can handle patient treatment, GUI 18 processing, data logging, and external communications. Safety module 58 may monitor control unit 4 to ensure that control unit 4 is functioning as intended. Safety module 58 may be located remotely from control unit 4. Safety module 58 may also communicate with a pressure sensor 60 located on at least one of control unit 4, tubing set attachment 8, tubing set 36, and catheter 44. Both control unit 4 and safety module 58 communicate with an audible alarm 62, a pinch valve 64, a pump 66, an air sensor 40, and a main battery 68, which powers control unit 4 and safety module 58.

[0065] The therapeutic process performed by system 2 may include the use of a drug or combination of drugs. In one embodiment, the drug or combination of drugs is administered to the patient by catheter 44 or system 2 of the present disclosure. In one embodiment, the combination of drugs includes at least two drugs. In another embodiment, the fluid administered by system 2 is a physiological fluid. That is, physiological fluids (generally without limitation and well known to those skilled in the art), such as 0.9% saline or lactated Ringer's solution, may be administered (and selectively aspirated) by catheter 44 of the present disclosure. In another embodiment, the fluid is a nutritional fluid.

[0066] System 2 can manage the flow rates of infused and aspirated fluids through catheter 44, which can be a multi-lumen catheter or a dual single-lumen catheter. As described above, control unit 4 is a software-based management system that uses specific algorithms to control pumps and sensors and ensure proper fluid delivery. Infusion and aspirated flow rate management can be implemented through valve functions that alternately restrict and allow fluid flow, and therefore fluid pressure, to the tubing, catheter, distal lumen, distal port, target tissue, or cavity. In the present disclosure, valves can be used to manage aspirated fluids, while infused fluids are managed through pump functions. Valve functions are driven by control unit 4 according to an algorithm and a desired therapy. Here, the protocol implemented by the controller, pump, and valves includes a programmed, alternating sequence of infusions, aspirates, and pauses in any combination appropriate for the therapy. During any of these flow rate phases, control unit 4 operates pump 66 and valves to determine the flow rate, fluid pressure, and cavity pressure within the system. The valve is configured to act on the tubing set 32 ​​as a pinch valve 64 and allow the tubing set 32 ​​to be inserted, threaded, or fed through the valve into the control unit 4. The valve itself is configured to function as a pinch valve 64 by being axially displaced relative to the tubing, for example, a linear solenoid. The valve may also be configured as a cantilever mechanism, roller mechanism, wedge, or tubing deflection mechanism.

[0067] The programmed treatment phases may be used to infuse fluid into and / or aspirate fluid from the cavity. During the treatment phases, the control unit 4 may sequence various user-selected treatment parameters to transition between different infusion and aspiration phases. The control unit 4 is configured to supply and direct fluid from the fluid source 10 through the tubing set 36 to the patient, e.g., into the patient's intracranial cavity, during the infusion phase. The control unit 4 is configured to drain fluid, e.g., from the intracranial cavity, through the tubing set 36 to the drainage receptacle 12 during the aspiration phase. The pump 66 of the control unit 4 may generate positive pressure within the tubing set 36, or a particular lumen thereof, to deliver fluid to the patient during the infusion phase, and may generate negative pressure within the tubing set 36, or a particular lumen thereof, to drain fluid from the patient during the aspiration phase. Exemplary infusion and aspiration programs include those discussed in U.S. Pat. No. 8,398,581 and U.S. Patent Application Publication No. 2015 / 0224284, the disclosures of which are incorporated herein by reference.

[0068] The control unit 4 may be preprogrammed to switch between the injection and suction phases based on the desired outcome from the healthcare professional. In other embodiments, the control unit 4 may switch between the injection and suction phases based on pressure measurements recorded by the pressure sensors 50, 60. In particular, the pressure sensors 50, 60 can transmit intracranial pressure ("ICP") measurements to the control unit 4, thereby monitoring the patient's ICP level. If the ICP measurement is within a desired range, the control unit 4 continues to implement the preprogrammed treatment process. If the ICP measurement exceeds a high ICP level setting, the control unit 4 may be configured to initiate a suction phase to drain the patient's intracranial cavity to lower the ICP. After a sufficient amount of fluid has been drained from the intracranial cavity and the ICP level has fallen below the high ICP level setting, the control unit 4 may be configured to resume the preprogrammed treatment process. In other embodiments, if the ICP measurement falls below a low ICP level setting, the control unit 4 may be configured to initiate an injection phase to introduce additional fluid into the patient's intracranial cavity. After fluid is introduced into the intracranial cavity and the ICP measurement exceeds the low ICP level setting, the control unit 4 may be configured to resume the preprogrammed therapy process. In other embodiments, a therapy stop event on the control unit 4 will cause the system 2 to return to a standby state. A therapy stop event may be initiated by a medical professional pressing a start / stop button. It is also contemplated that the control unit 4 may automatically return to a standby state in the event of an emergency involving the control unit 4 and / or the patient.

[0069] In one embodiment, the control unit 4 can transition between the infusion and aspiration states using several different techniques. In one embodiment, the pressure sensors 50, 60 can measure a first pressure value in the intracranial cavity and transmit this measurement to the control unit 4. An infusion of fluid into the intracranial cavity can then be initiated by the control unit 4. After the infusion phase, the pressure sensors 56, 60 can measure a second pressure value in the intracranial cavity and transmit this measurement to the control unit 4. The CPU of the control unit 4 can then calculate or determine the difference between the first and second pressure measurements from the pressure sensors 56, 60. If the difference between the first and second pressures exceeds a high threshold level, the control unit 4 can issue a high pressure signal output. The control unit 4 can then initiate an aspiration phase to reduce the ICP. If the difference between the first and second pressures falls below a low threshold level, the control unit 4 can issue a low pressure signal output. The control unit 4 can then initiate an infusion phase to increase the ICP.

[0070] Examples of fluid exchange catheter systems that can be used to perform the methods disclosed herein are those disclosed in one or more of U.S. Patent Nos. 8,398,581, 9,623,177, 10,293,105, and 11,123,483, the entire contents of each of which are incorporated herein by reference. Another example of a fluid exchange catheter system that can be used to perform the methods disclosed herein is that disclosed in U.S. Patent Application Publication No. 2020 / 0237977, the entire contents of which are incorporated herein by reference. Another example of a fluid exchange catheter system that can be used to perform the methods disclosed herein is the IRRAflow® Active Fluid Exchange System (AFES) offered by IRRAS. AFES is an intracranial fluid exchange system intended for use by medical hospital personnel, such as in neurosurgical procedures. Another example of a catheter component that can be used in the systems and methods described herein is any multi-lumen catheter containing more than one lumen. wherein one lumen is configured as an aspiration lumen and a second lumen is configured as an infusion lumen. Yet another example of a catheter component may be a combination of two or more separate catheters, a first catheter configured as an aspiration / drainage catheter and a second catheter configured as an infusion catheter. In certain non-limiting embodiments, the aspiration / drainage catheter is configured to drain from the distal end of the cavity, and the infusion catheter is configured to infuse from the proximal (opposite) end of the cavity.

[0071] 7 and 8, an example catheter 44 for use in system 2 is shown and described. Catheter 44 may include various features focused on achieving the desired infusion and aspiration functions of system 2. Some of these features are shown and described in U.S. Patent Application Publication No. 2015 / 0224284, the disclosure of which is incorporated herein by reference in its entirety. For purposes of this disclosure, the tip of catheter 44 that is inserted into biological material, e.g., the body of a patient, will be referred to as the distal tip or end of catheter 44, and the tip that remains outside of the biological material will be referred to as the proximal tip or end of catheter 44.

[0072] As shown in FIG. 9 , the catheter 44 may be a dual-lumen catheter. The catheter 44 may include an infusion lumen 104 and an aspiration lumen 106, each formed by one or more lumen walls generally extending from the proximal end of the catheter to the distal tip 108. It should be understood that certain lumens, i.e., the infusion lumen 104 and the aspiration lumen 106, may be interchanged. In one embodiment, the infusion lumen 104 may function as the outer catheter body. In one embodiment, the infusion lumen 104 and the aspiration lumen 106 diverge from each other at an intermediate location in the catheter 44. In one embodiment, the aspiration lumen 106 may be defined along the length of the catheter 44 where the infusion lumen 104 and the aspiration lumen 106 converge within the infusion lumen 104. In one embodiment, infusion fluid from the fluid source 10 is conducted through the infusion lumen 104. In one embodiment, fluid aspirated from the intracranial cavity into the drainage receptacle 12 is conducted through the aspiration lumen 106. However, infusion lumen 104 and aspiration lumen 106 are each structurally configured so that infusion or aspiration occurs therein depending on the particular flow direction permitted by the device attached to its proximal end.

[0073] As shown in FIG. 10 , the distal tip 108 of the catheter 44 may include a plurality of holes 110, commonly described as openings or ports, and / or may be porous. These holes 110 are designed to achieve desired performance for the infusion of therapeutic fluids and the evacuation of fluids and solids of various natures into the target tissue, which may arise in relation to the treatment of the disease or therapy being delivered. The holes 110 serve a multifaceted role of allowing optimal rates of both fluid infusion and fluid aspiration while maintaining a free and unimpeded flow rate through the system 2. Specific design factors that affect the performance of the holes 110 at the distal tip 108 include, for example, the size of the holes 110, their location within the catheter length or tip 108, their location relative to the target or surrounding tissue during use, their location relative to the aspiration lumen 106 of the catheter 44, the direction of fluid flow into and out of the aspiration lumen 106 relative to the holes 110, and the flow cross-sectional area of ​​the holes 110 relative to the flow area of ​​the aspiration lumen 106. These characteristics affect, among other things, the ability of catheter 44 to perform its infusion and aspiration functions as specified and desired.

[0074] The catheter 44, tubing set 36, and infusion / aspiration functions of system 2 may include one or more sensors as part of the electronic control system to achieve desired functionality and flow rates. These may include sensors located at the tip of the catheter, on the inner flow surface of the lumen, external to the lumen (in contact with the cavity or surrounding tissue), appropriately integrated along the length of the catheter lumen, tubing, cassette, and / or integrated into the fluid container to achieve desired flow control, biophysical feedback, and to gather biochemical information from the patient. These sensors may be positioned to monitor pressure, flow rate, pump function, intracavity pressure, tissue properties, pH, and other parameters. For example, pressure sensors may be positioned both internally and externally on the catheter 44 to measure the pressure differential between the cavity and the infusion and / or aspiration fluid. As a further example, pressure sensors may be positioned both internally and externally on the catheter 44 to measure the temperature differential between the cavity and the infusion and / or aspiration fluid. One or more MEMS-based sensors may also be included to measure fluid velocity within the catheter 44 and determine whether a higher fluid velocity is needed to break up solids in the aspirated fluid and / or whether a lower velocity is needed, for example, for aspirating a low viscosity fluid.

[0075] 11 , in one non-limiting embodiment, the fluid exchange catheter system 2 includes a spinal drainage line 112, such as a drainage catheter, that can be placed in the patient's spinal column. This allows fluids, such as fluids infused into the brain and / or CNS, to be drained from the spinal column. The spinal drainage line 112 can be inserted into the spinal column as a "spinal tap." This spinal drainage line 112 can be in addition to or instead of the suction function of the catheter 44 described above. The spinal drainage line 112 can be in fluid communication with the drainage receptacle 12 described above. This allows fluids drained from the spinal column via the spinal drainage line 112 to be collected in the drainage receptacle 12. Alternatively, fluids drained from the spinal drainage line 112 can be collected at a separate drainage point, such as a spinal drainage receptacle 114, that is not attached to or connected to the IV pole 6. For example, the spinal drainage receptacle 114 may be in fluid communication with the spinal drainage line 112, such as via one or more tubing sets. The spinal drainage receptacle 114 may be located remotely from other features of the fluid exchange catheter system 2. Drainage through the spinal drainage line 112 may be assisted by a pump that generates negative pressure within the spinal drainage line 112. The pump may be similar to pump 66 and may be located along the spinal drainage line 112 or at the drainage receptacle 114. Drainage may occur by gravity, for example, by placing the spinal drainage line 112 at a point lower than the patient's head, or by other means.

[0076] In one aspect of the present disclosure, the fluid exchange catheter system 2 can be used to manipulate one or more body characteristics, such as one or more physiological biomarkers. This manipulation can be achieved using the fluid exchange catheter system 2, specifically by placing the catheter 44 in a target region of the body, injecting fluid into the target region, and then draining the fluid from the region either directly through the catheter 44 or, alternatively, through a separate drainage mechanism, such as a spinal drainage line 112 placed in the spine. A "target region" can be a cavity or a specific portion of a cavity. In some non-limiting embodiments, the target region is the brain or a specific portion of the brain. In other non-limiting embodiments, the target region is the spine, abdomen, lungs, or a specific portion thereof. A target region can also be a combination of locations and / or cavities.

[0077] In one non-limiting embodiment, the present disclosure is directed to a method of promoting cooling of a target region, such as the brain, using a fluid exchange catheter system 2. In this embodiment, the fluid exchange catheter system 2 can deliver a fluid (e.g., saline or other cooling fluid, including hypotonic, hypertonic, or isotonic solutions) that promotes cooling of the target region. Additionally, one or more sensors (e.g., probes) of the fluid exchange catheter system 2 can monitor ICP, temperature, and other parameters (e.g., oxygen) in the target region, for example, via pressure sensors 56, 60 and temperature sensors 76, 78.

[0078] In this embodiment, the fluid exchange catheter system 2 may further include a cooling unit 88. The cooling unit 88 is configured to reduce the temperature of the cooling fluid (e.g., the fluid source 10) to a target value before the fluid reaches the patient. In one example, the cooling unit 88 includes one or more ice bath containers or ice packs. The tubing set 36 through which the cooling fluid passes may be immersed in one or more ice bath containers or surrounded by one or more ice packs along at least a portion of its length, for example, at two or three locations along its length. The ice bath containers and / or ice packs cool the fluid contained in the tubing set 36 as the cooling fluid passes from the fluid source 10 through the tubing set 36.

[0079] In another non-limiting embodiment, cooling unit 88 includes a heat exchange device, such as a freezer or refrigerator, in which fluid source 10 is housed. The heat exchange device can be set to a target temperature to cool or heat the fluid in fluid source 10 to this target temperature. Tube set 36 can be insulated to limit temperature changes in the cooling fluid as it flows through tubing set 36 after exiting cooling unit 88.

[0080] In yet other embodiments, the cooling unit 88 may be at or near the catheter 44. The tubing set 36 may enter a heat exchanger, where the contained fluid may be cooled or heated by heat exchange. The fluid may then exit the heat exchanger and enter the catheter 44 directly or through another length of the tubing set 36.

[0081] The fluid used to facilitate cooling of the target region (e.g., the fluid in fluid source 10) can be saline or other cooling fluid. In one non-limiting embodiment, the fluid is a cooling fluid designed to mimic a patient's CSF. For example, the cooling fluid can contain at least 99% water, along with various elements such as sodium, potassium, calcium, magnesium, chloride, and glucose, at levels at or near those of typical CSF. The osmolality and pH can also be adjusted to be in or near the range of CSF, typically with an osmolality of about 300 mOsm / L and a pH in the range of 7.25-7.5 (e.g., 7.33). In some non-limiting embodiments, a sample of a particular patient's CSF can be taken, and the contents of the cooling fluid can be adjusted to more closely resemble that of the particular patient's CSF.

[0082] As described above, in some non-limiting embodiments, fluid delivery can also provide for direct and / or continuous delivery of various types and combinations of drugs to a target region. Delivery of such drugs can be achieved, for example, by including drugs in the fluid in the fluid source 10 (e.g., fluid) delivered according to the methods described herein. Non-limiting examples of injectable drugs include thrombolytic drugs, antibiotics, other physician-prescribed injectable drugs, and combinations thereof, including drugs and therapeutic agents that can help reduce inflammation, such as anti-inflammatory drugs (e.g., corticosteroids), or drugs that can reduce metabolism. Other non-limiting examples of drugs can include biological agents, such as viruses and genes. As described above, cellular metabolism can cause breakdown / destruction as a result of injury, and reducing the metabolic rate within cells can reduce or limit this breakdown / destruction.

[0083] The target temperature of the fluid during infusion into a patient should be lower than the temperature of the patient's brain and / or CSF. This temperature is typically around 37°C, but may range from 39 to 40°C if the patient is experiencing other medical conditions, such as fever or inflammation. The temperature of the cooling fluid is not necessarily limited to a specific value, but it should not be lower than the crystallization temperature of the fluid itself and / or the temperature at which components of the fluid begin to change phase or separate from the fluid. Exemplary target temperatures for the cooling fluid can be between 0°C and 30°C, e.g., 10°C and 25°C, or 15°C and 20°C. In one specific example, the target temperature for the cooling fluid can be around 19°C. However, as noted above, the target temperature can be lower and approach 0°C, e.g., between 0°C and 10°C. Because a colder cooling fluid can absorb more heat per unit volume, lowering the temperature of the cooling fluid reduces the volume of cooling fluid required to achieve a target level of cooling within the body. In some non-limiting embodiments, the target temperature of the cavity (e.g., brain or CNS) can be achieved more quickly by utilizing cooling fluid at a lower target temperature (e.g., closer to the crystallization temperature) and by controlling the volume of cooling fluid. In the event of brain injury, the body responds by producing more CSF at a higher temperature (thus generating more heat). The volumetric flow rate of cooling fluid can then be selected and / or gradually increased to account for the rise in heat within the brain and CNS.

[0084] In the example of selective brain cooling, treatment can begin by preparing the fluid exchange catheter system. This preparation involves installing the tubing system in the control unit, preparing the tubing, calibrating the pressure sensors, and entering the patient's treatment settings. Concurrently, catheter components can be positioned in the target region (skull), secured in place with sutures, and tested. Probes can be inserted into the target region near the catheter components (e.g., adjacent to or integrated into the catheter components) to measure temperature and, optionally, oxygen levels, pH, and other biomarkers. The tubing system can then be connected to the catheter components, and the height of the control unit can be adjusted to align with the patient's ear canal (e.g., above the eyebrows) prior to initiating delivery of cooling fluid to and / or removal of fluid from the brain. In cavities (e.g., the brain) where overpressure is a critical parameter requiring strict control, it may be preferable to remove (drain) the fluid before initiating fluid infusion (reflux). For other, less sensitive regions, the order of fluid removal and infusion may be less critical.

[0085] In some non-limiting embodiments, the treatment method may be continued until physiological biomarkers reach target values. In the cooling embodiments described above, exemplary temperature targets for the brain or CNS may be 25°C to 36°C, e.g., 30°C to 35°C, or 32°C to 34°C. The target temperature may be 2 to 15°C, e.g., 3 to 9°C, 4 to 8°C, or 4.5 to 7.5°C, below the initial or baseline temperature of the brain. Different locations in the brain may be cooled to different levels, which may depend on the location of the injection point. For example, the target temperature of the contralateral hemisphere may be higher than the ipsilateral temperature. As an example, the target temperature in the contralateral hemisphere may be 1.5 to 4°C, e.g., 2 to 3°C, below baseline. In contrast, the ipsilateral temperature may be 3 to 9°C, e.g., 4.5 to 7.5°C, below baseline. An exemplary pH target may be 3.0 to 8.0. The pH of the cavity may be affected by the selected infusion fluid. The treatment method may be continued until inflammation is reduced by a clinically effective amount and / or until a reduction in inflammation is induced. The target temperature may be reached in approximately 1 hour, for example, 1 to 2 hours.

[0086] If the system 2 includes a spinal drainage line 112, the treatment method may further include draining the spent cooling fluid and / or CSF via the spinal drainage line 112 to a spinal drainage receptacle 114. This embodiment allows for rapid cooling of the patient's brain and / or CNS by circulating the CSF with the cooling fluid through "volume exchange." In a typical adult human, the total amount of CSF is approximately 150 mL. The method may include providing the patient with approximately the same amount of cooling fluid multiple times during the treatment period. In some non-limiting embodiments, the volumetric flow rate of the cooling fluid during the treatment period is 100-1000 mL / h, e.g., 200-800 mL / h.

[0087] The method of treatment may also include maintaining the brain or other cavity at a lower temperature for a set period of time, e.g., a predetermined time, followed by returning the temperature of the brain or other cavity to or near an initial / baseline temperature. For example, the method of treatment may include maintaining the brain or other cavity at a lower temperature (e.g., 33°C to 34°C) for a set period of time, such as 24, 48, or 72 hours. Such a lower temperature can be maintained by continuously circulating a cooling fluid according to the process described above. After the set period of time, the temperature can be increased, e.g., by a steady increase of 0.05°C to 0.2°C, e.g., 0.1°C per hour, until the brain or other cavity returns to a normal temperature of 37°C. The temperature can be increased by circulating an increased-temperature cooling fluid. For example, the temperature of the cooling fluid in this step can be at or near (e.g., within 2-3°C) normal human body temperature.

[0088] In the above-described methods, temperature can be monitored by one or more sensors, including temperature sensors 76, 78. These may be part of catheter system 2 or may be separate sensors, such as probe sensors inserted into the brain or other body region, to measure and monitor temperature so that a target temperature is achieved and maintained. System 2 may be adapted to automatically supply additional cooling fluid and / or provide an alarm or other visual or audio indicator to the operator, such as audible alarm 62, when the measured temperature exceeds the target temperature by a threshold value (e.g., 0.25-1°C).

[0089] Experimental verification The objective of this experimental study was to test the hypothesis that active exchange of CSF with chilled NaCl and acetated Ringer's solution could selectively reduce brain temperature without altering core body temperature in pigs.

[0090] The validation method was as follows: A double-lumen external ventricular drainage (EVD) catheter was inserted into the lateral ventricle of four pigs. A spinal drainage line was added to facilitate exchange of cerebrospinal fluid with chilled NaCl solution (one pig) or acetated Ringer's solution (three pigs). Brain parenchymal temperature was measured from the contralateral and ipsilateral hemispheres. CSF was exchanged with chilled fluid at rates ranging from 180 ml / h to 720 ml / h in four pigs. In two pigs, extensive stroke was induced endovascularly by occluding major cerebral arteries for 20 minutes.

[0091] The results of the study were as follows: The temperature of the contralateral hemisphere decreased by 2.2 to 3.1°C from baseline, while the core temperature changed only 0.5°C. The ipsilateral temperature decreased by 4.5 to 7.5°C from baseline to 29.9 to 33.8°C, while the average core temperature was 37.7°C. The total time required to achieve selective cooling was highly dependent on CSF flow rate and ranged from 10 minutes to 1.5 hours. One pig began to experience arrhythmias when its brain temperature approached 30.8°C, and in this case, CSF exchange with NaCl was performed. The other three pigs did not experience similar adverse events with acetated Ringer's solution. In two pigs with induced stroke, selective brain cooling was achieved despite a median poststroke arterial pressure of 140 mmHg. Selective brain cooling is possible with CSF exchange using a dual-lumen EVD, which creates a significant temperature difference between the core and brain.

[0092] Those skilled in the art can make modifications and variations to these embodiments without departing from the scope and spirit of the present disclosure. For example, it should be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment can be combined with one or more features of any other embodiment. Accordingly, the foregoing description is intended to be illustrative rather than limiting. The invention described herein is defined by the appended claims, and all modifications of the invention that come within the meaning and range of equivalency of the claims are embraced within their scope.

Claims

1. 1. A method for selectively varying the temperature of a cavity from a reference temperature to a target temperature different from said reference temperature, comprising: (a) turning on an infusion mechanism to infuse fluid into the cavity via a first fluid pathway and an infusion lumen in a catheter component for an infusion time, the fluid being brought to a target fluid temperature before reaching the cavity; (b) periodically or continuously removing at least a portion of the fluid via a second fluid path; (c) monitoring the temperature of the cavity; (d) maintaining the target temperature for a predetermined period of time; A method for providing

2. the cavity is the brain; The method of claim 1.

3. the fluid is a refrigerated fluid and is brought to the target fluid temperature using a cooling unit selected from the group consisting of one or more ice packs, one or more ice bath containers, a freezer, and a refrigerator; The method according to claim 1 or 2.

4. The target temperature is 30°C to 35°C. The method according to any one of claims 1 to 3.

5. The target temperature is 4°C to 8°C lower than the reference temperature. The method according to any one of claims 1 to 4.

6. The target fluid temperature is 15°C to 20°C. The method according to any one of claims 1 to 5.

7. The predetermined time is 24 hours to 72 hours. The method according to any one of claims 1 to 6.

8. the second fluid pathway is a drainage line placed in the spinal column; The method according to any one of claims 1 to 7.

9. the drainage line drains the fluid to a drainage receptacle; The method of claim 8.

10. the second fluid path is an aspiration lumen in the catheter component; The method according to any one of claims 1 to 9.

11. The catheter component is a dual lumen catheter or a dual single lumen catheter. The method according to any one of claims 1 to 10.

12. further comprising gradually returning the cavity to a temperature within 1-2°C of the reference temperature. The method according to any one of claims 1 to 11.

13. Gradually returning the cavity to a temperature within 1-2°C of the reference temperature comprises increasing the cavity temperature by 0.05°C to 0.2°C per hour. The method of claim 12.

14. the fluid has a composition substantially similar to that of cerebrospinal fluid; The method according to any one of claims 1 to 13.

15. The fluid is lactated Ringer's solution or saline. The method according to any one of claims 1 to 14.

16. the fluid comprises one or more anti-inflammatory drugs; The method according to any one of claims 1 to 15.

17. providing a visual or audio indicator if the monitored temperature differs from the target temperature by a threshold value. The method according to any one of claims 1 to 16.

18. The method is performed on a patient suffering from neuroinflammation. The method according to any one of claims 1 to 17.

19. The method is performed on a patient at risk for neuronal necrosis and / or ischemic brain injury. The method according to any one of claims 1 to 18.

20. 1. A system for altering the temperature of a cavity, comprising: a catheter system comprising a fluid set and a catheter component adapted for insertion into said cavity; a fluid source containing a fluid; an infusion mechanism comprising a pump adapted to deliver the fluid from the fluid source to the catheter component; a drainage line adapted to remove at least a portion of the fluid; one or more temperature sensors adapted to measure a temperature within the cavity; a heat exchange unit adapted to heat or cool the fluid before it reaches the cavity; A system comprising:

21. the drainage line is a spinal drainage line adapted for insertion into the patient's spine; 21. The system of claim 20.

22. the heat exchange unit is a cooling unit selected from the group consisting of one or more ice packs, one or more ice bath containers, a freezer, and a refrigerator; 22. A system according to claim 20 or 21.

23. The catheter component is a dual lumen catheter or a dual single lumen catheter. A system according to any one of claims 20 to 22.

24. 1. A method of manipulating a state of one or more physiological biomarkers within a target region of a cavity using a fluid exchange catheter system, comprising: The fluid exchange catheter system includes a catheter component having a plurality of fluid paths, an aspiration mechanism, and an infusion mechanism; a first fluid pathway defined by a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end; a second fluid pathway defined by a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end; the suction mechanism is operably connected to the proximal end of the first lumen; the injection mechanism is operably connected to the proximal end of the second lumen; The method comprises: (a) with the aspiration mechanism off, turning on the injection mechanism to inject an injection fluid through the first fluid pathway into the target area of ​​the cavity of the patient for an injection time or injection volume; (b) turning off the injection mechanism to stop the injection; (c) with the injection mechanism off, turning on the aspiration mechanism to aspirate fluid from the target area of ​​the patient through the second fluid path for an aspiration time or aspiration volume; (d) turning off the suction mechanism to stop suction; (e) repeating steps (a) to (d); Equipped with Steps (a) through (d) do not have to be performed in any particular order; method.

25. Steps (c) and (d) precede steps (a) and (b), such that the aspiration precedes the injection.

25. The method of claim 24.

26. Steps (a) and (b) precede steps (c) and (d), such that the infusion precedes the aspiration; 25. The method of claim 24.

27. The catheter component is a dual lumen catheter or a dual single lumen catheter. The method according to any one of claims 24 to 26.

28. The physiological biomarker(s) include temperature, intracranial pressure, pH, oxygen, sodium, glucose, creatinine, carbon dioxide, chloride, protein, or similar attributes in blood or cerebrospinal fluid chemistry, and combinations thereof; 28. The method according to any one of claims 24 to 27.

29. The infusion fluid is selected from the group consisting of saline, lactated Ringer's solution, or other physician-prescribed fluids. The method according to any one of claims 24 to 28.

30. further comprising injecting a drug into the cavity via one or more of the fluid pathways.

30. The method according to any one of claims 24 to 29.

31. the infusion fluid includes the drug; 31. The method of claim 30.

32. The drug is selected from the group consisting of a thrombolytic drug, an antibiotic, or other infusional drug prescribed by a physician, or a combination thereof.

31. The method of claim 30.

33. the cavity is the brain; 33. The method according to any one of claims 24 to 32.

34. The infusion fluid is infused into the ventricular system of the brain.

34. The method of claim 33.

35. Steps (a) through (d) are repeated until target levels of temperature, pH, and / or other relevant biomarkers are achieved within the target region of the cavity; The method according to any one of claims 24 to 34.

36. The patient is suffering from neuroinflammation. The method according to any one of claims 24 to 35.

37. the patient is at risk of neuronal necrosis and / or ischemic brain damage; The method according to any one of claims 24 to 36.

38. Steps (a) through (d) are repeated until inflammation is reduced by a clinically effective amount.

38. The method according to any one of claims 24 to 37.

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