Systems and methods for manipulating body characteristics using fluid exchange conduits

Abstract

Methods of selectively changing a temperature of a body lumen from a baseline temperature to a target temperature different from the baseline temperature are described. The method includes activating an infusion mechanism to infuse fluid into the body cavity through a first fluid path in the catheter assembly and an infusion lumen for an infusion period of time. The fluid reaches a target fluid temperature before reaching the body cavity. The method further includes periodically or continuously removing at least a portion of the fluid through a second fluid path, monitoring a temperature of the body cavity, and maintaining the target temperature for a predetermined period of time.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 382,396, filed on November 4, 2022, the entire content of which is hereby incorporated by reference in its entirety.

[0003] Background

[0004] Field

[0005] The present disclosure generally relates to methods and systems for manipulating body properties or biomarkers (such as temperature or pH) using a fluid exchange catheter system.

[0006] Description of Related Technologies

[0007] Therapeutic hypothermia (“TH”), which prevents or reduces irreversible neuronal necrosis and ischemic brain injury, has been shown to be effective in preventing ischemia - reperfusion injury in post - cardiac arrest syndrome and neonatal encephalopathy in both animal studies and clinical trials. However, reducing the whole - body temperature below 34°C can lead to serious systemic complications, such as cardiac side effects, blood side effects, immune side effects, and metabolic side effects. Although the brain accounts for only 2% of the total body weight, it consumes 20% of the total body energy at rest and requires continuous supply of glucose and oxygen to maintain functional and structural integrity. Selective brain cooling (“SBC”) with temperature control may be more beneficial for cerebral ischemia than systemic whole - body ischemia. Various SBC methods have been introduced to selectively cool the brain while minimizing systemic TH - related complications. However, technical hindrances of conventional SBC, such as insufficient cooling capacity and relatively expensive coolants and / or irritating effects on the skin or mucosal interface, limit its application in various clinical settings.

[0008] Acute brain injury can cause distal organ damage even in the absence of systemic disease or inflammation. Since this type of injury affects not only the brain but also the whole body, a holistic treatment approach may be required. Although systemic TH can help reduce this type of brain injury, it may lead to systemic complications that affect the biological survival process. Inducing and maintaining systemic hypothermia in warm-blooded mammals causes physiological side effects, and some of these side effects can lead to morbidity and death. The side effects of TH can be systematically classified into cardiac complications, immune complications, and metabolic complications. Common adverse events of TH may include hyperglycemia, shivering, bradycardia, electrolyte abnormalities, acute kidney injury, pneumonia, and hypercoagulable or hypocoagulable state syndromes. The physiological adverse events caused by systemic TH require specialized intensive care resources, sedatives and muscle relaxants, mechanical ventilators, and combinations thereof. Therefore, these physiological complications should be carefully considered and closely monitored in the intensive care unit, and patients considering TH should be admitted to the intensive care unit. This requirement may be another obstacle to the application of systemic TH. Recently, drug-induced hypothermia has received attention 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 the treatment of stroke in conscious subjects, even when initiated quite some time after re-infusion. The combined treatment of pharmacological and physical TH methods may effectively reduce side effects by reducing the drug dose and the time required to reach the treatment target.

[0009] SBC can be performed in three ways to achieve the target temperature in patients with acute brain injury. The three main mechanisms of SBC are as follows: (1) direct surface cooling of the scalp; (2) intravascular cooling, which enables heat exchange between the internal carotid artery and intracranial venous drainage; and (3) intranasal cooling, which enables rapid heat exchange in the upper airway.

[0010] In addition to temperature, the manipulation of other body parameters, properties, and biomarkers can also provide important physiological advantages.

[0011] The following references provide additional background and are also expressly incorporated herein by reference:

[0012] ·Hong,et al.,“Selective Brain Cooling:A New Horizon ofNeuroprotection,”Front.Neurol.,20June 2022,Sec.Endovascular andInterventional Neurology,vol.13(2022). https: / / doi.org / 10.3389 / fneur.2022.873165

[0013] ·Mattingly,et al.,“The Complex Relationship Between CoolingParameters and Neuroprotection in a Model of Selective Hypothermia,”Front.Neurol.,25April 2022,Sec.Endovascular and Interventional Neurology,vol.13(2022). https: / / doi.org / 10.3389 / fneur.2022.874701

[0014] ·Horn,et al.,“Non-invasive Brain Temperature Measurement in AcuteIschemic Stroke,”Front.Neurol.,05August 2022,Sec.Endovascular andInterventional Neurology,vol.13(2022). https: / / doi.org / 10.3389 / fneur.2022.889214

[0015] ·Wang,et al.,“Updates on Selective Brain Hypothermia:Studies FromBench Work to Clinical Trials,”Front.Neurol.,06May 2022,Sec.Endovascular andInterventional Neurology,vol.13(2022). https: / / doi.org / 10.3389 / fneur.2022.899547

[0016] ·Magnoni,et al.,“A Novel Cooling Device for Targeted BrainTemperature Control and Therapeutic Hypothermia:Feasibility Study in anAnimal Model,”Neurocrit Care,December 2016,vol.25,issue 3,pages464-472,doi:10.1007 / s12028-016-0257-7,PMID:26927280,PMCID:PMC5138276.

[0017] · 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 Overview

[0018] To at least meet the above needs, the present disclosure provides a method for selectively changing the temperature of a body cavity from a baseline temperature to a target temperature different from the baseline temperature. The method includes activating an infusion mechanism to infuse a fluid through a first fluid path and an infusion lumen in a catheter assembly into the body cavity for an infusion period of time. The fluid reaches a target fluid temperature before reaching the body cavity. The method further includes periodically or continuously removing at least a portion of the fluid through a second fluid path, monitoring the temperature of the body cavity, and maintaining the target temperature for a predetermined period of time.

[0019] In another aspect, the present disclosure provides a system for changing the temperature of a body cavity. The system includes a catheter system that includes a fluid set and a catheter assembly adapted to be inserted into the body cavity. The system further includes a fluid source that contains a fluid; an infusion mechanism that includes a pump adapted to pump the fluid from the fluid source to the catheter assembly; a drainage line that is adapted to remove at least a portion of the fluid; one or more temperature sensors that are adapted to measure the temperature in the body cavity; and a heat exchange unit that is adapted to heat or cool the fluid before the fluid reaches the body cavity.

[0020] In another aspect, the present disclosure provides a method of manipulating the state of one or more physiological biomarkers within a target region of a body cavity using a fluid exchange catheter system. The fluid exchange catheter system includes a catheter assembly having a plurality of fluid paths. A first fluid path is formed by a first lumen having a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end. A second fluid path is formed by a second lumen having a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end. The system further includes a suction 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 (a) activating the infusion mechanism to infuse an infusion fluid through the first fluid path and into a target region of a patient's body cavity for an infusion period of time or to an infusion volume while the suction mechanism is deactivated; (b) deactivating the infusion mechanism to stop the infusion; (c) activating the suction mechanism to aspirate fluid from the target region of the patient through the second fluid path for a suction period of time or to a suction volume while the infusion mechanism is deactivated;

[0021] (d) deactivating the suction mechanism to stop the aspiration; and (e) repeating steps (a) through (d). Steps (a) through (d) need not be performed in any particular order.

[0022] The invention is also disclosed in the following clauses.

[0023] Clause 1. A method of selectively changing the temperature of a body cavity from a baseline temperature to a target temperature different from the baseline temperature, the method comprising:

[0024] (a) activating an infusion mechanism to infuse a fluid through a first fluid path and an infusion lumen in a catheter assembly into the body cavity for an infusion period of time, wherein the fluid reaches a target fluid temperature before reaching the body cavity;

[0025] (b) periodically or continuously removing at least a portion of the fluid through a second fluid path;

[0026] (c) monitoring the temperature of the body cavity; and

[0027] (d) maintaining the target temperature for a predetermined period of time.

[0028] Clause 2. The method according to clause 1, wherein the body cavity is the brain.

[0029] Clause 3. The method according to clause 1 or 2, wherein the fluid is a cooling fluid, and a cooling unit selected from the following is used to bring the fluid to the target fluid temperature: one or more ice packs, one or more ice baths, a freezing device, and a refrigeration device.

[0030] Clause 4. The method according to any one of Clauses 1-3, wherein the target temperature is 30°C to 35°C.

[0031] Clause 5. The method according to any one of Clauses 1-4, wherein the target temperature is 4°C to 8°C lower than the baseline temperature.

[0032] Clause 6. The method according to any one of Clauses 1-5, wherein the target fluid temperature is 15°C to 20°C.

[0033] Clause 7. The method according to any one of Clauses 1-6, wherein the predetermined time period is 24 hours to 72 hours.

[0034] Clause 8. The method according to any one of Clauses 1-7, wherein the second fluid path is a drainage pipeline disposed in the spine.

[0035] Clause 9. The method according to Clause 8, wherein the drainage pipeline drains the fluid into a drainage container.

[0036] Clause 10. The method according to any one of Clauses 1-9, wherein the second fluid path is a suction lumen in the catheter.

[0037] Clause 11. The method according to any one of Clauses 1-10, wherein the catheter assembly is a double-lumen catheter or a duplicity of single-lumen catheters.

[0038] Clause 12. The method according to any one of Clauses 1-11, further comprising gradually returning the body cavity to a temperature within 1°C to 2°C of the baseline temperature.

[0039] Clause 13. The method according to Clause 12, wherein gradually returning the body cavity to a temperature within 1°C to 2°C of the baseline temperature includes increasing the temperature of the body cavity by 0.05°C to 0.2°C per hour.

[0040] Clause 14. The method according to any one of Clauses 1-13, wherein the composition of the fluid is substantially equivalent to the composition of cerebrospinal fluid.

[0041] Clause 15. The method according to any one of Clauses 1-14, wherein the fluid is lactated Ringer's solution or saline fluid.

[0042] Clause 16. The method according to any one of Clauses 1-15, wherein the fluid contains one or more anti-inflammatory drugs.

[0043] Clause 17. The method according to any one of Clauses 1-16 further includes providing a visual or audible indicator if the monitored temperature differs from the target temperature by a threshold amount.

[0044] Clause 18. The method according to any one of Clauses 1-17, wherein the method is performed on a patient suffering from neuroinflammation.

[0045] Clause 19. The method according to any one of Clauses 1-18, wherein the method is performed on a patient at risk of neuronal necrosis and / or ischemic brain injury.

[0046] Clause 20. A system for altering the temperature of a body cavity, comprising: a catheter system including a fluid set and a catheter assembly adapted to be inserted into the body cavity; a fluid source containing a fluid; an infusion mechanism including a pump adapted to pump the fluid from the fluid source to the catheter assembly; a drainage line adapted to remove at least a portion of the fluid; one or more temperature sensors adapted to measure the temperature in the body cavity; and a heat exchange unit adapted to heat or cool the fluid before it reaches the body cavity.

[0047] Clause 21. The system according to Clause 20, wherein the drainage line is a spinal drainage line adapted to be inserted into a patient's spine.

[0048] Clause 22. The system according to Clause 20 or 21, wherein the heat exchange unit is a cooling unit selected from: one or more ice packs, one or more ice baths, refrigeration devices, and cold storage devices.

[0049] Clause 23. The system according to any one of Clauses 20-22, wherein the catheter assembly is a double-lumen catheter or two single-lumen catheters.

[0050] Article 24. A method of manipulating the state of one or more physiological biomarkers within a target region of a body cavity using a fluid exchange catheter system, wherein the fluid exchange catheter system comprises: a catheter assembly including a plurality of fluid paths, wherein a first fluid path is formed by a first lumen having a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end, and wherein a second fluid path is formed by a second lumen having a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end; a suction 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 comprising: (a) while the suction mechanism is deactivated, activating the infusion mechanism to infuse an infusion fluid through the first fluid path and into a target region of the patient's body cavity for an infusion time period or to an infusion volume; (b) deactivating the infusion mechanism to stop the infusion; (c) while the infusion mechanism is deactivated, activating the suction mechanism to aspirate fluid from the target region of the patient through the second fluid path for a suction time period or to a suction volume; (d) deactivating the suction mechanism to stop the suction; and (e) repeating steps (a) through (d), wherein steps (a) through (d) do not need to be performed in any particular order.

[0051] Article 25. The method according to Article 24, wherein steps (c) and (d) precede steps (a) and (b) such that the suction precedes the infusion.

[0052] Article 26. The method according to Article 24, wherein steps (a) and (b) precede steps (c) and (d) such that the infusion precedes the suction.

[0053] Article 27. The method according to any one of Articles 24 - 26, wherein the catheter assembly is a dual-lumen catheter or two single-lumen catheters.

[0054] Article 28. The method according to any one of Articles 24 - 27, wherein the one or more physiological biomarkers include temperature, intracranial pressure, pH, oxygen, sodium, glucose, creatinine, carbon dioxide, chloride, protein, or similar attributes of the chemical composition of blood or cerebrospinal fluid, and combinations thereof.

[0055] Article 29. The method according to any one of Articles 24 - 28, wherein the infusion fluid is selected from: saline, lactated Ringer's solution, or other prescription fluids prescribed by a physician.

[0056] Article 30. The method according to any one of Articles 24 - 29, further comprising: infusing a drug into the body cavity through one or more of the fluid paths.

[0057] Clause 31. The method according to Clause 30, wherein the infusion fluid comprises the drug.

[0058] Clause 32. The method according to Clause 30, wherein the drug is selected from: thrombolytics, antibiotics, or other prescription drugs prescribed by a physician for infusion, or a combination thereof.

[0059] Clause 33. The method according to any one of Clauses 24 - 32, wherein the body cavity is the brain.

[0060] Clause 34. The method according to Clause 33, wherein the infusion fluid is infused into the ventricular system of the brain.

[0061] Clause 35. The method according to any one of Clauses 24 - 34, wherein steps (a) to (d) are repeated until the temperature, pH, and / or other relevant biomarkers within the target region of the body cavity are at target levels.

[0062] Clause 36. The method according to any one of Clauses 24 - 35, wherein the patient has neuroinflammation.

[0063] Clause 37. The method according to any one of Clauses 24 - 36, wherein the patient is at risk of neuronal necrosis and / or ischemic brain injury.

[0064] Clause 38. The method according to any one of Clauses 24 - 37, wherein steps (a) to (d) are repeated until the inflammation is reduced by a clinically effective amount.

[0065] With reference to the accompanying drawings, these and other features and characteristics of the present disclosure will become more apparent after considering the following description and the appended claims, all of which form a part of this specification. Brief Description of the Drawings

[0067] Figure 1 is a perspective view of a fluid exchange system according to one aspect of the present disclosure;

[0068] Figure 2 is Figure 1 a left perspective view of the control unit of the fluid exchange system of

[0069] Figure 3 is Figure 2 a right perspective view of the control unit of

[0070] Figure 4 is Figure 2 a rear view of the control unit of

[0071] Figure 5 is Figure 1 a front view of the tube set attachment of the fluid exchange system of

[0072] Figure 6 is Figure 1 a schematic view of an operating system of a fluid exchange system;

[0073] Figure 7 is a perspective view of a catheter according to one aspect of the present disclosure;

[0074] Figure 8 is Figure 7 a cross-sectional view of the catheter;

[0075] Figure 9 is a cross-sectional view taken along line A-A of Figure 7 the distal tip of the catheter;

[0076] Figure 10 is a perspective view of the distal tip of a catheter according to one aspect of the present disclosure; and

[0077] Figure 11 is a perspective view of a configuration using a spinal drainage line according to one aspect of the present disclosure.

[0078] Detailed description

[0079] For purposes of the description below, spatial orientation terms shall relate to the orientation of the embodiments in the figures. However, it should be understood that various embodiments of the present disclosure may take alternative variations and step sequences, unless expressly stated to the contrary. It should also be understood that the specific devices and processes shown in the figures and described in the following specification are merely exemplary. Accordingly, specific dimensions and other physical characteristics related to the embodiments disclosed herein should not be considered limiting.

[0080] As used in this specification, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0081] Unless otherwise indicated, all ranges or ratios disclosed herein shall be understood to include any and all subranges or subratios subsumed therein. For example, the range or ratio "1 to 10" shall be considered to include any and all subranges between the minimum value 1 and the maximum value 10, inclusive; that is, all subranges or subratios starting with a minimum value of 1 or more and ending with a maximum value of 10 or less, such as but not limited to 1 to 6.1, 3.5 to 7.8, and 5.5 to 10.

[0082] Unless otherwise indicated, all documents mentioned herein, such as but not limited to issued patents and patent applications, are hereby incorporated by reference in their entirety.

[0083] Methods and systems are provided for manipulating one or more physiological properties or biomarkers of a bodily portion of a body cavity 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 properties in the chemical composition of blood or cerebrospinal fluid, and combinations thereof.

[0084] 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 the spine / spinal cord) in order to change (e.g., decrease or increase) their temperature. A fluid exchange catheter system can also remove fluid from the CNS (e.g., by draining), which can be, for example, the patient's spent cooling fluid and / or cerebrospinal fluid (“CSF”). Removal can ensure that additional fluid can be added without increasing pressure. The methods and systems disclosed herein can achieve targeted, selective manipulation of bodily properties. For example, the methods and systems described herein can achieve targeted cooling of the brain and / or CNS without causing the same cooling effect in other portions of the body (e.g., other organs, such as the heart or lungs), or at least without causing the same degree of cooling in these other portions of the body. A decrease in temperature in the brain or other bodily portion can provide various advantages, including reducing edema (stretching tissue and allowing it to remain structurally intact) 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 the target region provides additional benefits because it can avoid whole body hypothermia and problems that can be caused by cooling the heart, lungs, arteries, and other bodily portions.

[0085] Reference Figure 1, Fluid exchange system 2 according to a non-limiting embodiment of the present disclosure is shown and described. In one aspect, system 2 includes a control unit 4, a tubing set attachment 8, a fluid source 10, and a drainage container 12 that are connected to an intravenous (IV) pole 6 or other support structure. The control unit 4, the drainage container 12, and the fluid source 10 can be connected to the IV pole 6 using any suitable connecting device for securing the control unit 4 and the drainage container 12 to the IV pole 6. The fluid source 10 and the drainage container 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 container 12 is a suction bag. The fluid source 10 can be positioned above the tubing set attachment 8 and direct fluid to the tubing set attachment 8. The drainage container 12 can be positioned below the tubing set attachment 8 and receive fluid from the patient and drained through the tubing set attachment 8. System 2 also includes a tubing set 36 and a cooling unit 88, which will be described below.

[0086] Reference Figures 2 - 6 , The control unit 4 of system 2 is shown and described in more detail. The control unit 4 can be a computer-based management system that utilizes, for example, software and / or firmware to implement pump and sensor control and the proper delivery of fluids. The software and / or firmware can include algorithms in the form of programming instructions stored on a non-transitory machine-readable medium associated with system 2. The programming instructions can be executed by a processor associated with the control unit 4 to enable the control unit 4 to perform the various tasks and methods discussed herein.

[0087] The control unit 4 can include a pump 66 that is configured to direct fluid through the tubing set attachment 8. The pump 66 can be configured to direct fluid from the fluid source 10 through the tubing set attachment 8 to the patient. The pump 66 can also be configured to drain fluid from the patient's body through the tubing set attachment 8 and into the drainage container 12 by creating or generating a negative pressure in the tubing set attachment 8. Pumps suitable for the present disclosure are generally known. In one aspect, the pump 66 is a peristaltic pump. The control unit 4 can also include a pinch valve to control the flow of fluid through the tubing set attachment 8. The pump 66 and the pinch valve can be held within the housing 14 of the control unit 4. The control unit 4 can also include a connection port 16 to receive the tubing set attachment 8.

[0088] The control unit 4 may also include a graphical user interface (GUI) 18 to display control options, alert indications, and system parameters regarding the system 2 to the patient or medical staff. In one aspect, the GUI 18 includes an LCD touch screen display to allow the medical staff to operate the control unit 4. The control unit 4 also includes a central processing unit (CPU) configured to operate a 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 operation parameters and alert indications of the control unit 4.

[0089] The system 2 may also include a flow sensor, algorithms, and related methods for controlling pump motor functions, for example, to achieve precise control of infusions in terms of volume, rate, duration, post-infusion pause periods, and pressure measurement intervals, thereby delivering fluids, pharmaceuticals, altering tissue effects and responses, achieving desired therapeutic effects, meeting safety requirements, managing the patency of the catheter 44 and tubing set 36, and achieving desired flow characteristics. For example, the flow sensor may be a MEMS-based flow sensor or an impeller-driven flow meter.

[0090] Continuing to refer Figure 3 to, the control unit 4 may also include a drainage container hanger 32 configured to hold the drainage container 12. In one aspect, the drainage container 12 is a suction bag. The drainage container hanger 32 may include a graduated measuring tape 34 that is connected to the control unit 4 at one end and to the drainage container 12 at the opposite end. The graduated measuring tape 34 allows the drainage container 12 to be vertically adjusted relative to the control unit 4. The graduated measuring tape 34 may also indicate the vertical distance between the control unit 4 and the drainage container 12. When the drainage container 12 is vertically adjusted relative to the control unit 4, the medical staff can determine the vertical distance between the drainage container 12 and the control unit 4, or in another aspect, determine the vertical distance between the drainage container 12 and the patient's head positioned adjacent to the system 2. In one aspect, the graduated measuring tape 34 includes measurement values (such as inches, centimeters, etc.) provided thereon that identify the vertical distance between the drainage container 12 and the control unit 4.

[0091] Refer Figure 6, the configuration of the operating system of system 2 is shown and described according to a non-limiting embodiment. The control unit 4 can communicate with various data sources, including the keyboard and / or touch screen 46 of the GUI 18, the pressure sensor calibration knob 42, the real-time clock calendar 48, the flash memory 50, the USB host 52, and the service port 54. In one aspect, the control unit 4 also communicates with at least one pressure sensor 56 configured to record measurements of the fluid pressure in system 2. In one aspect, the pressure sensor 56 can be positioned on at least one of the following: the control unit 4, the tubing set attachment 8, and the conduit 44. In another aspect, one or more temperature sensors 76, 78 can be positioned on at least one of the following: the tubing set attachment 8, the tubing set 36, and the conduit 44. In another aspect, the control unit 4 also communicates with a safety module 58. The control unit 4 can manipulate patient treatment, GUI 18 processing, data recording, and external communication. The safety module 58 can monitor the control unit 4 to ensure that the control unit 4 operates as expected. The safety module 58 can be located remotely from the control unit 4. The safety module 58 can also communicate with a pressure sensor 60 disposed on at least one of the following components: the control unit 4, the tubing set attachment 8, the tubing set 36, and the conduit 44. Both the control unit 4 and the safety module 58 communicate with an audible alarm 62, a pinch valve 64, a pump 66, an air sensor 30, and a main battery 68 that powers the control unit 4 and the safety module 58.

[0092] The treatment process performed by system 2 can include the use of a drug or drug combination. In one aspect, the drug or drug combination is administered to a patient through the conduit 44 of the present disclosure or system 2. In one aspect, the drug combination comprises at least two drugs. In another aspect, the fluid administered by system 2 is a physiological fluid. That is, a physiological fluid (which is generally unrestricted and well-known to those skilled in the art), such as 0.9% NaCl or lactated Ringer's fluid, can be administered (and optionally aspirated) through the conduit 44 of the present disclosure. In other aspects, the fluid is a nutritional fluid.

[0093] System 2 can manage the flow of infused and aspirated fluids through catheter 44, which can be a multi-lumen catheter or two single-lumen catheters. As mentioned above, control unit 4 is a software-based management system that uses certain algorithms to implement pump and sensor control and the proper delivery of fluids. Infusion and aspiration flow management can be performed through valve functions that can alternately restrict and allow fluid flow, thus restricting and allowing fluid pressure to flow to tubes, catheters, distal lumens, distal ports, target tissues, and body cavities. In the present disclosure, valves can be used to manage aspirated fluids, while infused fluids are managed by pump functions. The valve functions are manipulated by control unit 4 according to algorithms and desired treatments, where the protocols performed by the controller, pump, and valves include programmed, alternating sequences of infusion, aspiration, and pauses, in the form of any suitable treatment combination thereof. During any of these flow phases, control unit 4 operates the pump 66 and valves to determine flow rates, fluid pressure within the system, and body cavity pressure. The valve is constructed in such a way that it acts as a pinch valve 64 on tube set 32 and also allows tube set 32 to be inserted, threaded, or fed into control unit 4 and through the valve. The valve itself is configured to act as a pinch valve 64 by axial displacement against the tube, for example, as a linear solenoid. The valve can also be configured as a cantilever mechanism, a roller mechanism, a wedge, or a tube deflection mechanism.

[0094] Programmed treatment states can be used to infuse and / or aspirate fluids into and from a body cavity. When in a treatment state, control unit 4 can vary between different infusion and aspiration states by user-selected different treatment parameter sequences. During the infusion state, control unit 4 is configured to supply fluid from fluid source 10 through tube set 36 and direct it to the patient, for example, to the patient's intracranial cavity. During the aspiration state, control unit 4 is configured to drain fluid from, for example, the intracranial cavity through tube set 36 and into drainage container 12. Pump 66 of control unit 4 can create positive pressure in tube set 36 or its specific lumen to pump fluid to the patient during the infusion state, and can create negative pressure in tube set 36 or its specific lumen to drain fluid from the patient during the aspiration state. Exemplary infusion and aspiration procedures include those discussed in U.S. Patent No. 8,398,581 and U.S. Patent Application Publication No. 2015 / 0224284, the disclosures of which are incorporated herein by reference.

[0095] The control unit 4 can be pre-programmed to switch between the infusion and aspiration states based on the desired outcome of the medical staff. On the other hand, the control unit 4 can switch between the infusion and aspiration states based on the pressure readings recorded by the pressure sensors 56, 60. In particular, the pressure sensors 56, 60 can send intracranial pressure ("ICP") readings to the control unit 4, and the control unit 4 monitors the ICP level of the patient. In the case where the ICP reading is within the desired range, the control unit 4 continues to run the pre-programmed treatment process. In the case where the ICP reading exceeds the high ICP level setting, the control unit 4 can be configured to initiate the aspiration state to drain fluid from the patient's intracranial cavity to reduce the ICP. After a sufficient volume of fluid has been drained from the intracranial cavity and the ICP level has decreased between the high ICP level settings, the control unit 4 can be configured to resume the pre-programmed treatment process. On the other hand, in the case where the ICP reading drops below the low ICP level setting, the control unit 4 can be configured to initiate the infusion state to direct additional fluid into the patient's intracranial cavity. After the fluid has been directed into the intracranial cavity and the ICP reading has increased above the low ICP level setting, the control unit 4 can be configured to resume the pre-programmed treatment process. On the other hand, a treatment stop event of the control unit 4 will cause the system 2 to return to the ready state. The treatment stop event can be initiated by the medical staff pressing the start / stop button. It is also conceivable that in the case of an emergency situation with the control unit 4 and / or the patient, the control unit 4 can automatically return to the ready state.

[0096] In one aspect, the control unit 4 can vary between the infusion and aspiration states using several different techniques. In one aspect, the pressure sensors 56, 60 can measure a first pressure value in the intracranial cavity and send the measured value to the control unit 4. Then, the infusion of fluid into the intracranial cavity can be initiated by the control unit 4. After the infusion state, the pressure sensors 56, 60 can measure a second pressure value in the intracranial cavity and send the measured value to the control unit 4. Then, the CPU of the control unit 4 can calculate or determine the difference between the first pressure reading and the second pressure reading from the pressure sensors 56, 60. In the case where the difference between the first pressure and the second pressure exceeds the high threshold level, the control unit 4 can issue a high-pressure signal output. Then, the control unit 4 can initiate the aspiration state to reduce the ICP. In the case where the difference between the first pressure and the second pressure is below the low threshold level, the control unit 4 can issue a low-pressure signal output. Then, the control unit 4 can initiate the infusion state to increase the ICP.

[0097] Example 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. Other examples of fluid exchange catheter systems that can be used to perform the methods disclosed herein are those 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 provided by IRRAS Active Fluid Exchange System (AFES). The AFES is an intracranial fluid exchange system designed to be used by medical hospital staff, such as in neurosurgical medical care. Another example of a catheter assembly that can be used in the systems and methods described herein is any multi-lumen catheter that includes more than one lumen, where one lumen is configured to be a suction lumen and a second lumen is configured to be an infusion lumen. Yet another example of a catheter assembly can be a combination of two or more separate catheters, where the first separate catheter is configured to be a suction / drainage catheter and the second separate catheter is configured to be an infusion catheter. In certain non-limiting embodiments, the suction / drainage catheter can be configured to drain from the distal end of a body cavity, and the infusion catheter can be configured to infuse through the proximal (opposite) end of the body cavity.

[0098] Reference Figure 7 and Figure 8 , examples of the catheter 44 used in the system 2 are shown and described. The catheter 44 can include a variety of features focused on achieving the desired infusion and suction functions of the system 2. Several 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 the purposes of this disclosure, the tip of the catheter 44 inserted into a biological material, such as a patient's body, is referred to as the distal tip or distal end of the catheter 44, while the tip remaining outside the biological material is referred to as the proximal tip or proximal end of the catheter 44.

[0099] As Figure 9As shown, catheter 44 can be a dual-lumen catheter. Catheter 44 can include an infusion lumen 104 and a suction lumen 106, each formed by one or more lumen walls that generally extend from the proximal end of catheter 44 to the distal tip 108. It should be understood that the specific lumens, i.e., infusion lumen 104 and suction lumen 106, can be switched. In one aspect, infusion lumen 104 can serve as the outer catheter body. In one aspect, the infusion and suction lumens 104, 106 branch from each other at an intermediate location on catheter 44. In one aspect, suction lumen 106 can be defined within infusion lumen 104 along the length of catheter 44, where infusion lumen 104 and suction lumen 106 converge within catheter 44. In one aspect, infusion fluid from fluid source 10 is directed through infusion lumen 104. In one aspect, fluid aspirated from the intracranial cavity into drainage container 12 is directed through suction lumen 106. However, infusion lumen 104 and suction lumen 106 are each structurally configured to allow infusion or aspiration to occur therein, depending on the specific flow direction achieved by the device attached to its proximal end.

[0100] As Figure 10 As shown, the distal tip 108 of catheter 44 can include a plurality of holes 110 and / or can have porosity, generally described as openings or ports. These holes 110 are designed to achieve the desired performance for infusing therapeutic fluids and evacuating fluids and solids from the target tissue, as well as various features that may occur in the context of disease treatment or the treatment being delivered. The holes 110 serve multiple purposes to allow for optimal rates of fluid infusion and fluid aspiration, as well as to maintain free, unobstructed flow through system 2. Specific design elements that affect the performance of holes 110 in distal tip 108 are, for example, the size of holes 110, the location of holes 110 along the catheter length or tip 108, the location of holes 110 relative to the target or surrounding tissue during use, the location of holes 110 relative to suction lumen 106 of catheter 44, the direction of fluid flowing into and out of suction lumen 106 relative to holes 110, and the cross-sectional flow area of holes 110 relative to the flow area of suction lumen 106. These features, among others, affect the ability of catheter 44 to perform its infusion and aspiration functions as specified and desired.

[0101] The infusion and aspiration functions of the catheter 44, tubing set 36, and system 2 may also include one or more sensors as part of an electronic control system to achieve the desired functions and flow rates. These may include sensors placed within the catheter tip, on the internal flow surface of the lumen, on the exterior of the lumen (in contact with the body cavity or surrounding tissue), along the catheter lumen, tubing, appropriately integrated along the length of the cassette, and / or within the fluid container to achieve the desired flow control, biophysical feedback, and collection of biochemical information from the patient. These sensors may be arranged to monitor pressure, flow rate, pump function, pressure within the body cavity, tissue properties, pH, and other parameters. For example, pressure sensors may be placed inside and outside the catheter 44 to measure the pressure differential between the body cavity and the infused and / or aspirated fluid. As another example, temperature sensors may be placed inside and outside the catheter 44 to measure the temperature differential between the body cavity and the infused and / or aspirated fluid. Additionally, one or more MEMS-based sensors may be included to measure the 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 suitable for aspiration of, for example, low viscosity fluids, etc.

[0102] Reference Figure 11 , in a non-limiting embodiment, the fluid exchange catheter system 2 includes a spinal drainage line 112 (e.g., a drainage catheter) that may be placed in the patient's spine to allow fluid (e.g., fluid infused into the brain and / or CNS) to drain from the spine. The spinal drainage line 112 may be inserted into the spine as a "spinal tap." The spinal drainage line 112 may be supplementary to or in place of the aspiration function of the catheter 44 described above. The spinal drainage line 112 may be in fluid communication with the drainage container 12 described above such that fluid drained from the spine through the spinal drainage line 112 may be collected in the drainage container 12. Alternatively, fluid drained from the spinal drainage line 112 may be collected at a separate drainage location (e.g., a spinal drainage container 114) that is not attached or connected to the IV pole 6. For example, the spinal drainage container 114 may be in fluid communication with the spinal drainage line 112, e.g., through one or more tubing sets. The spinal drainage container 114 may be located separately from other aspects of the fluid exchange catheter system 2. Drainage through the spinal drainage line 112 may be assisted by a pump that creates a negative pressure within the spinal drainage line 112. The pump may be similar to the pump 66 and may be co-linearly arranged with the spinal drainage line 112 or located at the drainage container 114. Drainage may also occur by gravity, e.g., by placing the spinal drainage line 112 at a point lower than the patient's head, or by other means of drainage.

[0103] In one aspect of the present disclosure, the fluid exchange catheter system 2 can be used to manipulate one or more body characteristics, e.g., one or more physiological biomarkers. Such manipulation can be achieved by using the fluid exchange catheter system 2 and, in particular, by placing the catheter 44 into a target region of the body and infusing fluid into the target region and then draining the fluid directly from the region through the catheter 44 or through a separate drainage mechanism (e.g., a spinal drainage line 112 placed in the spine) from the region. The "target region" can be a body cavity or a specific part of a body cavity. In some non-limiting embodiments, the target region is the brain or a specific part of the brain. In other non-limiting embodiments, the target region is the spine, abdomen, or lungs or specific parts thereof. The target region can also be a combination of locations and / or body cavities.

[0104] In one non-limiting embodiment, the present disclosure relates to a method of using the fluid exchange catheter system 2 to promote cooling of a target region (e.g., the brain). In this embodiment, the fluid exchange catheter system 2 can deliver a fluid (e.g., saline or other cooling fluid, including hypo-osmotic, hyper-osmotic, or iso-osmotic fluids) 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, e.g., via pressure sensors 56, 60 and temperature sensors 76, 78.

[0105] In this embodiment, the fluid exchange catheter system 2 can additionally include a cooling unit 88 configured to reduce the temperature of the cooling fluid (e.g., 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 baths or ice packs. The tube set 36 through which the cooling fluid passes can be immersed in one or more ice baths or surrounded by one or more ice packs at at least a portion of its length, e.g., at two or three locations along its length. As the cooling fluid passes from the fluid source 10 through the tube set 36, the ice bath / ice pack cools the fluid contained within the tube set 36.

[0106] In another non-limiting embodiment, the cooling unit 88 includes a heat exchange device, e.g., a refrigeration or a chilling device, in which the fluid source 10 is housed. The heat exchange device can be set to a target temperature to cool or heat the fluid within the fluid source 10 to that target temperature. The tube set 36 can be insulated to limit temperature changes of the cooling fluid as it flows through the tube set 36 after leaving the cooling unit 88.

[0107] In yet another embodiment, the cooling unit 88 can be at or near the conduit 44. The tube bundle 36 can enter a heat exchanger where the fluid contained in the tube bundle 36 can be cooled or heated by heat exchange. The fluid can then leave the heat exchanger and enter the conduit 44 directly or through another length of the tube bundle 36.

[0108] The fluid used to facilitate cooling of the target region (e.g., the fluid in the fluid source 10) can be saline or another 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 include at least 99% water and various elements at or near typical CSF levels, such as sodium, potassium, calcium, magnesium, chloride, and glucose. The osmotic pressure and pH can also be adjusted to the CSF range or near it, typically with an osmotic pressure of about 300 mOsm / L and a pH of 7.25 to 7.5 (e.g., 7.33). In some non-limiting embodiments, a CSF sample from a particular patient can be collected and the cooling fluid contents can be adjusted to more closely align with the CSF of that particular patient.

[0109] As mentioned above, in some non-limiting embodiments, fluid delivery can additionally provide direct and / or continuous drug delivery of various types and combinations of drugs into the target region. Such drug delivery can be achieved, for example, by including the drug to be delivered along with the fluid in the fluid source 10 (e.g., the fluid) according to the methods described herein. Non-limiting examples of drugs that can be infused are thrombolytics, antibiotics, other physician-prescribed drugs for infusion, and combinations thereof, including drugs and therapeutic agents that can help reduce inflammation (e.g., anti-inflammatory drugs (e.g., corticosteroids)) or agents that can reduce metabolism. Other non-limiting examples of drugs can include biopharmaceuticals, such as viruses or genes. As mentioned, cellular metabolism can be disrupted / damaged due to injury, and reducing the intracellular metabolic rate can reduce or limit such disruption / damage.

[0110] The target temperature of the fluid when injected into a patient should be lower than the temperature of the patient's brain and / or CSF, which is typically about 37 °C, but may be 39 - 40 °C if the patient is experiencing a fever or other medical event (such as inflammation). While the temperature of the cooling fluid is not necessarily limited to a certain value, the temperature should not be lower than the crystallization temperature of the fluid itself and / or should not be lower than the temperature at which the components of the fluid begin to undergo a phase change or otherwise separate from the fluid. Example temperature target values for the cooling fluid can be from 0 °C to 30 °C, such as from 10 °C to 25 °C or from 15 °C to 20 °C. In one specific example, the temperature target value of the cooling fluid can be about 19 °C. However, as mentioned, the target value can be much lower and can approach 0 °C, such as from 0 °C to 10 °C. As the temperature of the cooling fluid decreases, the volume of the cooling fluid required to achieve the target cooling level in the body also decreases because the cooler fluid can absorb additional heat per unit volume. In some non - limiting embodiments, the target temperature of a body cavity (e.g., the brain or CNS) can be achieved more rapidly by using a cooling fluid at a low target temperature (e.g., near the crystallization temperature) and by controlling the volume of the cooling fluid. In some cases of brain injury, the body will respond by producing a higher volume of CSF at an elevated temperature (thereby generating additional heat), and the volume flow rate of the cooling fluid can be selected and / or gradually increased to address this increase in heat within the brain and CNS.

[0111] In an example of selective cooling of the brain, the treatment can begin by preparing a fluid exchange catheter system by mounting a tubing system to a control unit, priming the tubing, calibrating a pressure sensor, and entering patient treatment settings. At the same time, the catheter assembly can be placed in the correct position in the target area (skull), fixed in place with sutures, and tested. A probe can be inserted into the target area near (e.g., adjacent to or integrated with) the catheter assembly to measure temperature and optionally oxygen level, pH, and other biomarkers. Then, the tubing system can be connected to the catheter assembly, and the height of the control unit can be adjusted to align with the patient's external auditory canal (e.g., the top of the eyebrow) before beginning to deliver the cooling fluid to the brain and / or remove fluid from the brain. In some body cavities (e.g., the brain) where overpressure is an important parameter that needs to be tightly controlled, it may be preferred to remove (drain) fluid before beginning to infuse (irrigate) fluid. For other less sensitive areas, the order of fluid removal and infusion may not be as important.

[0112] In some non-limiting embodiments, the treatment method can continue until a physiological biomarker reaches a target value. In the cooling embodiments described above, exemplary temperature target values for the brain or CNS can be from 25°C to 36°C, such as from 30°C to 35°C or from 32°C to 34°C. The target temperature can also be 2 - 15°C lower than the initial or baseline temperature of the brain, such as 3 - 9°C, 4 - 8°C, or 4.5 - 7.5°C. Different parts of the brain can also be cooled to different levels, which can depend on the location of the injection site. For example, the target temperature in the contralateral cerebral hemisphere can be higher than the ipsilateral temperature. For instance, the target temperature in the contralateral cerebral hemisphere can be 1.5 - 4°C lower than the baseline, such as 2 - 3°C, while the ipsilateral temperature can be 3 - 9°C lower than the baseline, such as 4.5 - 7.5°C. Exemplary pH target values can be from 3.0 to 8.0. The pH value of the body cavity can be affected by the selected infusion fluid. The treatment method can also continue until the inflammation is reduced by a clinically effective amount and / or until inflammation reduction is induced. The method can also include controlling disrupted cytokines and electrolytes when there is brain injury. The target temperature can be reached in approximately 1 hour (e.g., 1 - 2 hours).

[0113] In cases where the system 2 includes a spinal drainage line 112, the treatment method can also include draining spent cooling fluid and / or CSF through the spinal drainage line 112 and into a spinal drainage container 114. This embodiment allows CSF and the cooling fluid to cycle through "volume exchange", thereby rapidly cooling the patient's brain and / or CNS. In a typical adult, the total volume of CSF is approximately 150 mL. The method can involve providing the patient with approximately equal volumes of cooling fluid multiple times during the treatment cycle. In some non-limiting embodiments, during the treatment process, the volumetric flow rate of the cooling fluid is from 100 mL / h to 1000 mL / h, such as from 200 mL / h to 800 mL / h.

[0114] The treatment method can also include returning the temperature of the brain or other body cavity to the initial / baseline temperature or a temperature close to the initial / baseline temperature after maintaining the brain or other body cavity at a lower temperature for a period of time (e.g., a pre-determined period of time). For example, the treatment method can include maintaining the brain or other body cavity at a lower temperature (e.g., 33°C to 34°C) for a set amount of time (e.g., 24 hours, 48 hours, or 72 hours). This lower temperature can be maintained by continuously circulating the cooling fluid according to the process described above. After the set amount of time has elapsed, the temperature can be increased (e.g., by steadily increasing by, for example, 0.05°C to 0.2°C per hour, such as 0.1°C) until the brain or other body cavity returns to a normal body temperature of 37°C. The increase in temperature can be achieved by circulating the cooling fluid with an increased temperature. For example, the temperature of the cooling fluid in this step can be at or close to (e.g., within 2 - 3°C) the normal human body temperature.

[0115] In the above method, the temperature can be monitored by one or more sensors, including temperature sensors 76, 78, which can be part of the catheter system 2 or separate sensors inserted into the brain or other body regions to measure and monitor the temperature and ensure that the target temperature is reached and maintained, such as probe sensors. If the measured temperature exceeds the target temperature by a threshold amount (e.g., 0.25 - 1 °C), the system 2 can also be adapted to automatically provide additional cooling fluid and / or provide an alert or other visual or audio indicator to the operator, such as an audible alarm 62.

[0116] Experimental Study

[0117] The aim of the experimental study was to test the hypothesis that by actively exchanging CSF for cooled NaCl and Ringer's acetate fluid, brain temperature could be selectively reduced without changing the core temperature of the pig body.

[0118] The research method was as follows. A double-lumen external ventricular drainage (EVD) catheter was inserted into the lateral ventricles of four pigs. A spinal drainage line was added to accelerate the exchange of CSF with cooled NaCl (one pig) or Ringer's acetate (three pigs) fluid. Brain parenchymal temperature was measured from the contralateral and ipsilateral cerebral hemispheres. CSF was exchanged for the cooled fluid at a rate of 180 ml - 720 ml / h in four pigs. In two pigs, global stroke was induced globally by closing the aorta of the brain for 20 minutes via an endovascular method.

[0119] The research results were as follows. The temperature of the contralateral cerebral hemisphere decreased by 2.2 - 3.1 °C from the baseline, while the core temperature changed only by 0.5 °C. The ipsilateral temperature cooled from the baseline by 4.5 - 7.5 °C to reach 29.9 - 33.8 °C, while the core temperature was on average 37.7 °C. The total time required to achieve selective cooling was highly dependent on the CSF rate and was from 10 min to 1.5 h. One pig started to show arrhythmia when the brain temperature approached 30.8 °C; in this case, the CSF exchange was carried out with NaCl fluid. The other three pigs using acetic acid Ringer's did not have similar adverse events. In the two stroke-induced pigs, selective brain cooling was achieved despite a median arterial pressure of 140 mmHg after the stroke. Selective brain cooling became possible via CSF exchange using a double-lumen EVD to achieve a significant temperature difference between the body core and the brain.

[0120] Those skilled in the art can make modifications and changes to these aspects 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 aspect can be combined with one or more features of any other aspect. Accordingly, the foregoing description is intended to be illustrative rather than restrictive. The invention described above is defined by the appended claims, and all changes to the invention that fall within the meaning and equivalents of the claims are included within the scope of the claims.

Claims

1. A method for selectively changing the temperature of a body cavity from a baseline temperature to a target temperature different from the baseline temperature, the method comprising: (a) activating an infusion mechanism to infuse a fluid through a first fluid path and an infusion lumen in a catheter assembly into the body cavity for an infusion time period, wherein the fluid reaches a target fluid temperature before reaching the body cavity; (b) periodically or continuously removing at least a portion of the fluid through a second fluid path; (c) monitoring the temperature of the body cavity; and (d) maintaining the target temperature for a predetermined time period.

2. The method according to claim 1, wherein the body cavity is the brain.

3. The method according to claim 1 or 2, wherein the fluid is a cooling fluid, and a cooling unit selected from the following is used to bring the fluid to the target fluid temperature: one or more ice packs, one or more ice baths, a freezing device, and a refrigeration device.

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

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

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

7. The method according to any one of claims 1-6, wherein the predetermined time period is 24 hours to 72 hours.

8. The method according to any one of claims 1-7, wherein the second fluid path is a drainage pipeline disposed in the spine.

9. The method according to claim 8, wherein the drainage pipeline drains the fluid into a drainage container.

10. The method according to any one of claims 1-9, wherein the second fluid path is a suction lumen in the catheter assembly.

11. The method according to any one of claims 1-10, wherein the catheter assembly is a double-lumen catheter or two single-lumen catheters.

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

13. The method according to claim 12, wherein gradually returning the body cavity to a temperature within 1 °C to 2 °C of the baseline temperature includes raising the temperature of the body cavity by 0.05 °C to 0.2 °C per hour.

14. The method according to any one of claims 1-13, wherein the composition of the fluid is substantially equivalent to the composition of cerebrospinal fluid.

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

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

17. The method according to any one of claims 1-16, further comprising providing a visual or auditory indicator if the monitored temperature differs from the target temperature by a threshold amount.

18. The method according to any one of claims 1-17, wherein the method is performed on a patient with neuroinflammation.

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

20. A system for altering the temperature of a body cavity, comprising: A catheter system comprising a fluid set and a catheter assembly adapted to be inserted into the body cavity; A fluid source containing a fluid; An infusion mechanism comprising a pump adapted to pump the fluid from the fluid source to the catheter assembly; A drainage line adapted to remove at least a portion of the fluid; One or more temperature sensors adapted to measure the temperature in the body cavity; And A heat exchange unit adapted to heat or cool the fluid before it reaches the body cavity.

21. The system according to claim 20, wherein the drainage line is a spinal drainage line adapted to be inserted into a patient's spine.

22. The system according to claim 20 or 21, wherein the heat exchange unit is a cooling unit selected from: one or more ice packs, one or more ice baths, refrigeration equipment, and cold storage equipment.

23. The system according to any one of claims 20-22, wherein the catheter assembly is a double-lumen catheter or two single-lumen catheters.

24. A method of manipulating the state of one or more physiological biomarkers within a target region of a body cavity using a fluid exchange catheter system, wherein the fluid exchange catheter system comprises: A catheter assembly comprising a plurality of fluid paths, wherein a first fluid path is formed by a first lumen having a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end, and wherein a second fluid path is formed by a second lumen having a proximal end, a distal end, and a lumen wall extending between the proximal end and the distal end; A suction 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 comprising: (a) When the suction mechanism is deactivated, activating the infusion mechanism to infuse an infusion fluid through the first fluid path and reach a target area of the patient's body cavity for an infusion time period or until an infusion volume is reached; (b) Deactivating the infusion mechanism to stop the infusion; (c) When the infusion mechanism is deactivated, activating the suction mechanism to suction fluid from the target area of the patient through the second fluid path for a suction time period or until a suction volume is reached; (d) Deactivating the suction mechanism to stop the suction; and (e) Repeating steps (a) to (d), wherein steps (a) to (d) do not need to be performed in any particular order.

25. The method according to claim 24, wherein steps (c) and (d) precede steps (a) and (b) such that the suction precedes the infusion.

26. The method according to claim 24, wherein steps (a) and (b) precede steps (c) and (d) such that the infusion precedes the suction.

27. The method according to any one of claims 24-26, wherein the catheter assembly is a double-lumen catheter or two single-lumen catheters.

28. The method according to any one of claims 24 - 27, wherein the one or more physiological biomarkers include temperature, intracranial pressure, pH, oxygen, sodium, glucose, creatinine, carbon dioxide, chloride, and protein, or similar properties in the chemical composition of blood or cerebrospinal fluid, and combinations thereof.

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

30. The method according to any one of claims 24-29, further comprising: Infusing a drug into the body cavity through one or more of the fluid paths.

31. The method according to claim 30, wherein the infusion fluid contains the drug.

32. The method according to claim 30, wherein the drug is selected from: thrombolytics, antibiotics, or other prescription drugs prescribed by a physician for infusion, or combinations thereof.

33. The method according to any one of claims 24 - 32, wherein the body cavity is the brain.

34. The method according to claim 33, wherein the infusion fluid is infused into the ventricular system of the brain.

35. The method according to any one of claims 24 - 34, wherein steps (a) to (d) are repeated until the temperature, pH, and / or other relevant biomarkers in the target region of the body cavity are at target levels.

36. The method according to any one of claims 24 - 35, wherein the patient has neuroinflammation.

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

38. The method according to any one of claims 24 - 37, wherein steps (a) to (d) are repeated until the inflammation is reduced by a clinically effective amount.

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