Patent Publication Number: US-2022226150-A1

Title: Endovascular Cooling Catheter System Which Employs Phase-Changing Heat Exchange Media

Description:
RELATED APPLICATION 
     This patent application claims priority to U.S. Provisional Patent Application No. 61/540,439 filed Sep. 28, 2011, the entire disclosure of which is expressly incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     This invention relates generally to devices and methods for medical treatment and more particularly to devices and methods for endovascular heat exchange for altering or controlling body temperature in a human or animal subject. 
     BACKGROUND OF THE INVENTION 
     Hypothermia can be induced in humans and some animals for the purpose of protecting various organs and tissues (e.g., hear, brain, kidneys) against the effects of ischemic, anoxic or toxic insult. For example, animal studies and/or clinical trials suggest that mild hypothermia can have neuroprotective and/or cardioprotective effects in animals or humans who suffer from ischemic cardiac events (e.g., myocardial infract, acute coronary syndromes, etc.), postanoxic coma after cardiopulmonary resuscitation, traumatic brain injury, stroke, subarachnoid hemorrhage, fever and neurological injury. Also, studies have shown that whole body hypothermia can ameliorate the toxic effects of radiographic contrast media on the kidneys (e.g., radiocontrast nephropathy) of patients with pre-existing renal impairment who undergo angiography procedures. 
     One method for inducing hypothermia is by endovascular temperature management (ETM) wherein a heat exchange catheter is inserted into a blood vessel and a thermal exchange fluid is then circulated through the heat exchange catheter. This technique can effectively cool blood flowing through the subject&#39;s vasculature and, as a result, lower the core body temperature of the subject to some desired target temperature. ETM is also capable of warming the body and/or of controlling body temperature to maintain a monitored body temperature at some selected temperature. If a controlled rate of re-warming or re-cooling from the selected target temperature is desired, that too can be accomplished by carefully controlling the amount of heat added or removed from the body and thereby controlling the temperature change of the patient. 
     In some situations, it is desirable to induce hypothermia rapidly. When blockage of an artery causes acute ischemia, such as is the case in acute myocardial infarction and ischemic stroke, a primary treatment objective is to reperfuse (i.e., restore blood flow to) the ischemic tissue within a short period of time (e.g., less than 5 hours) after the onset of acute clinical symptoms. Such reperfusion can be accomplished by surgery to remove or bypass the blockage or by catheter based interventions (e.g., angioplasty, stenting, atherectomy, catheter-based embolectomy, etc.) or through the use of thrombolytic drugs (e.g., tissue plasminogen activator (TPA) or streptokinase). It is currently believed that improved outcomes in such ischemic events may be achievable through the use of therapeutic hypothermia in combination with a reperfusion strategy such as surgery, catheter based intervention and/or thrombolytic drug therapy. For example, in one study, it was observed that the mean size of anterior wall myocardial infarctions is significantly reduced in patients whose core body temperature had been lowered to at least 35° C. prior to reperfusion of the infarct zone. This observation is not explained by other factors including time-to-presentation, lesion location and incidence of TIMI flow prior to angioplasty. Thus, evidence exists that the ability to induce hypothermia rapidly (i.e., prior to reperfusion) may be a critical factor in optimizing patient outcomes following acute ischemic events. 
     The present invention provides for rapid induction of hypothermia in ETM by using a heat exchange medium that undergoes an endothermic phase change as it circulates through the heat exchange catheter. 
     Matter primarily exists in four phases—solid, liquid, gas, and plasma—as well as a few other extreme phases such as critical fluids and degenerate gases. Generally, when a solid is warmed (or as pressure decreases), that solid will change to a liquid form and may eventually become a gas. For example, ice (frozen water) melts into liquid water when it is heated. As the water boils, the water evaporates and becomes water vapor. Sometimes, solids will transition directly from solid to gas, bypassing the liquid phase. This is known as sublimation. 
     Whenever a phase change occurs, energy is either absorbed or released. In exothermic phase changes, chemical potential energy is converted to heat energy, thereby resulting in a release of heat. In endothermic phase changes, heat energy is converted into chemical potential energy, thereby resulting in absorption of heat. Solid to liquid phase changes are typically endothermic. 
     The prior art has included certain heat exchange catheter systems wherein a volatile refrigerant is compressed to a liquid state, infused into a heat exchange catheter and allowed to expand within an expansion chamber, thereby undergoing an endothermic gas to liquid phase change. This gas to liquid phase change ostensibly results in absorption of heat to result in cooling of the subject&#39;s circulating blood and lowering of the subject&#39;s body temperature. Examples of heat exchange catheter systems wherein such gas-liquid phase change occurs are described in U.S. Pat. No. 6,149,677 (Dobak III, et al.), the entire disclosure of which is expressly incorporated herein by reference. The use of a compressed refrigerant to effect a gas to liquid phase change within an indwelling heat exchange catheter presents handling and processing issues as well as potential injury to the subject should the volatile refrigerant leak from the catheter into the subject&#39;s bloodstream. 
     There remains a need in the art for the development of new endovascular systems and methods for rapidly lowering a subject&#39;s body temperature in a safe and consistent manner. 
     SUMMARY OF THE INVENTION 
     Further details, aspects, elements and attributes of the present invention may be appreciated by those of skill in the art after reading the detailed description and examples set forth below. 
     In accordance with one aspect of the present invention, there is provided a heat exchange catheter or other body cooling device that is insertable into or positionable in contact with the body of a human or animal subject. Such catheter or other body cooling device has an inlet, an outlet and at least one lumen through which heat exchange medium may be circulated. The catheter is connected to a source of a heat exchange medium that comprises liquid phase matter and solid phase matter, wherein the solid phase matter has a melting point not higher than about 37 degrees C. and a pump or pressurization apparatus for circulating the heat exchange medium through the catheter or other body cooling device while it is inserted in or positioned on the body of a human or animal subject. During this process, at least some of the solid phase matter melts (i.e., undergoes a solid to liquid phase change), thereby removing heat from the heat exchange medium. 
     In accordance with another aspect of the present invention, there is provided a method for lowering the temperature of all or part of the body of a human or animal subject. Such method generally comprises the steps of A) positioning a heat exchange catheter or other heat exchange device in or on the subject&#39;s body; B) delivering into the catheter or other heat exchange device a flowable heat exchange medium such that it exchanges heat with the subject&#39;s body resulting in lowering of the temperature of all or part of the subject&#39;s body. The flowable heat exchange medium comprises solid phase matter that melts, either within the catheter or other heat exchange device or elsewhere within a heat exchange medium flow, path thereby removing heat from the heat exchange medium. The heat exchange medium does not directly contact or mix with any body fluid or tissue of the subject&#39;s body. 
     Further aspects, details, examples and embodiments of the invention will be appreciated by those of skill in the art upon reading the detailed description set forth below. 
    
    
     
       DETAILED DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a general diagram of an endovascular heat exchange system of the present invention comprising an extracorporeal control console and a heat exchange catheter, wherein a distal portion of the heat exchange catheter is operatively inserted into the vasculature of a human subject. 
         FIG. 2  is a schematic diagram on a first embodiment of a solid-liquid phase changing endovascular heat exchange system of the present invention. 
         FIG. 2A  is a cross sectional view through line  2 A- 2 A of  FIG. 2 . 
         FIG. 2B  is a cross sectional view through line  2 B- 2 B of  FIG. 2 . 
         FIG. 2C  is a cross sectional view through line  2 C- 2 C of  FIG. 2 . 
         FIGS. 2D and 2E  are schematic diagrams of one non-limiting example of a pump that may be used for pumping slurry in the system of  FIG. 2  or any other system of the present invention which incorporates a slurry pump. 
         FIG. 3  is a schematic diagram of a second embodiment of a solid-liquid phase changing endovascular heat exchange system of the present invention. 
         FIG. 4  is a schematic diagram of a third embodiment of a solid-liquid phase changing endovascular heat exchange system of the present invention. 
         FIG. 5  is a schematic diagram of a fourth embodiment of a solid-liquid phase changing endovascular heat exchange system of the present invention. 
         FIG. 5A  is a schematic sectional diagram of one non-limiting example of a slurry generating device useable in the system of  FIG. 5  or any other system of the present invention which incorporates a slurry generating device. 
         FIG. 5B  is a schematic sectional diagram of a slurry generating device of  FIG. 5A  positioned between cooling elements. 
         FIG. 6  is a schematic diagram of a fifth embodiment of a solid-liquid phase changing endovascular heat exchange system of the present invention. 
         FIG. 7  is a schematic drawing of a human subject having an alternative heat exchange catheter inserted in the subject&#39;s body. 
         FIG. 8  is a cross sectional view of one non-limiting example of an air separator that may be useable in those embodiments of the present invention that have air separators. 
         FIG. 9A  is a schematic diagram of one non-limiting type of a liquid/gas/solid detector that may optionally be incorporated into any of the systems of the present invention to measure the relative amounts of liquid phase matter (e.g., saline solution), solid phase matter (e.g., frozen particles) and gas (e.g., air bubbles). 
         FIG. 9B  is a schematic diagram of one non-limiting type of a liquid/gas/solid detector that may optionally be incorporated into any of the systems of the present invention to measure the relative amounts of liquid phase matter (e.g., saline), solid phase matter (e.g., frozen particles) and gas (e.g., air bubbles). 
     
    
    
     DETAILED DESCRIPTION 
     The following detailed description, the accompanying drawings and the above-set-forth brief descriptions of the drawings are intended to describe some, but not necessarily all, examples or embodiments of the invention. The contents of this detailed description, the accompanying drawings and the above-set-forth brief descriptions of the drawings do not limit the scope of the invention, or the scope of the following claims, in any way. 
     General Aspects of a Heat Exchange Catheter System Which Uses a Heat Exchange Slurry for Rapid Cooling of a Subject&#39;s Body 
       FIG. 1  is a diagrammatic example of a body temperature management system  10  of the present invention. In this example, the body temperature management system  10  generally comprises a heat exchange catheter  12  that is connected to extracorporeal component(s)  14 . A distal portion of the heat exchange catheter  16  is inserted into the vasculature of a human subject and positioned, in this example, so that a heat exchange region  18  of the catheter  16  is within the subject&#39;s inferior vena cava IVC. It is to be appreciated, however, that the catheter  16  and its heat exchange region  18  may be alternatively positioned in various other blood vessels, body lumens or body cavities, depending on the particular application and clinical setting in which the system is being utilized. 
     The extracorporeal component(s)  14  comprise, at minimum, a source of frozen solid/liquid heat exchange slurry and a pressure apparatus or pump for delivering that heat exchange slurry through inlet line  22  into an inflow lumen of the catheter  16 . The solid-liquid heat exchange slurry then circulates through the catheter&#39;s inflow lumen and through a heat exchanger  18  on the catheter whereby the heat exchange slurry exchanges heat with blood flowing through the subject&#39;s vasculature. This exchange of heat causes some or all of the solid phase of the slurry to melt and causes cooling of the subject&#39;s flowing blood. This cooling of the subject&#39;s flowing blood results in cooling of downstream organ(s) (e.g., the heart or brain) and/or cooling of the subject&#39;s whole body. The melting of some or all of the solid particles contained in the heat exchange slurry results in substantially more cooling of the subject&#39;s flowing blood than would be attained using a liquid heat exchange medium that is devoid of solid phase particles which melt during the heat exchange. In this manner, the present invention cools target organ(s) or the whole body more quickly than the endovascular heat exchange systems of the prior art which utilized cooled liquid heat exchange media. 
     In at least some embodiments of the present invention, the heat exchange medium (including any remaining solid phase particles that have not melted) may be circulated back from an outflow lumen of the catheter  16 , through return line  22 , and into a container within the extracorporeal system  14 . In this manner, any remaining solid particles may be circulated back through the catheter  16  alone or in combination with additional heat exchange slurry or temperature controlled liquid. 
     Composition and Preparation of Slurry 
     The heat exchange slurry may comprise any suitable mixture of frozen solid-phase particles and liquid-phase matter. Preferably, the heat exchange slurry will be sterile and sufficiently biocompatible to avoid serious injury to the subject if some or all of the slurry were to inadvertently leak from the catheter  12  into the subject&#39;s bloodstream or body. A slurry formed of frozen and liquid sodium chloride solution is one biologically compatible slurry that may be used in this invention. Examples of sterile saline slurries and their methods of manufacture are described in U.S. Pat. No. 7,389,653 (Kasza et al.) entitled  Medical Ice Slurry Production Device , the entire disclosure of which is expressly incorporated herein by reference. In some applications of the present invention, such as those where relatively small diameter heat exchange catheters are used, it may be desirable for the solid particles of the slurry to be very small in diameter and/or for the slurry to contain a lubricious composition (e.g., a glycol such as propylene glycol) to deter agglomeration of the solid particles and/or to facilitate flow of the slurry through small diameter catheter lumens. Also, in at least some embodiments, it may be desirable for the solid particles of the slurry to be substantially spherical, or at least devoid of sharp edges, to facilitate flow of the slurry through small or tortuous catheter lumens. 
     Slurries useable in this invention may be prepared using known technology, such as a slurry ice generator having a scraped-surface vertical shell and tube heat exchanger. The inner surface of an inner tube is wiped using a wiping mechanism that comprises a sealed, rotating central shaft that has spring-loaded plastic blades or brushes extending outwardly from the shaft. Small ice crystals that form near the tube surface are wiped away from the surface by the rotating blades or brushes and are mixed with unfrozen liquid, thereby forming the slurry. Fluidized bed heat exchangers may also be used wherein steel particles circulate with the fluid to mechanically remove the crystals from the surface heat exchanger surface. The steel particles are then separated from the resultant ice slurry. 
     Another type of slurry generator that may be used is known as a direct contact slurry generator. In such device, an immiscible primary refrigerant is caused to evaporate in a manner that supersaturates water and forms small smooth ice crystals. However, a small amount of refrigerant may remain in ice crystals formed by this method. 
     Yet another type of slurry generator that may be used is known as a supercooling generator. In such device, water is pressurized and supercooled to −2° C. and then released through a nozzle. As it exits the nozzle, the supercooled water changes from liquid phase to solid phase, thereby forming small ice particles. In some embodiments, grinding or other 
     In some embodiments, the heat exchange slurry may comprise phase change material (PCM) microcapsules disbursed in a liquid. Each PCM microcapsule comprises a core formed of phase changing material (e.g., frozen saline solution or other frozen liquid) and a shell which surrounds the core. PCM microcapsules have heretofore been reported to be useable in thermal management applications due to their ability to absorb and release large amounts of heat during phase change. Examples of PCM microcapsules and their methods of manufacture include, but are not limited to, those described in U.S. Pat. Nos. 4,911,232 (Colvin et al.); 6,703,127 (Davis, et al.) and 6,835,334 (Davis et al.) and United States Patent Application Publication Nos. 2003/0222378 (Xing et al.); 2004/0076826 (Lee et al.); 2004/0121072 (Xing et al.); 2006/0161232 (Kasza et al.); 20080193653 (Oh et al) and 2011/0008536 (Oh, et al), the entire disclosure of each such patent and published patent application being expressly incorporated herein by reference. 
     Catheter Based Cooling of a Subject&#39;s Body Using the Solid-Liquid Heat Exchange Slurry 
     The heat exchange slurry will typically be utilized for only an initial period of time or until the temperature of the organ(s) or whole body has been lowered to a target hypothermic temperature (e.g., 34-36 degrees C.). Thereafter, the system  10  may continue to control the temperature of the organ(s) or whole body by circulating a temperature controlled heat exchange liquid, such as 0.9% sodium chloride solution, through the catheter  16  in the same manner as heretofore accomplished by a number of commercially available endovascular heat exchange catheter systems, including the Thermogard XP Temperature Management System available from ZOLL Circulation of Sunnyvale, Calif. or the InnerCool RTx™ Endovascular System available from Philips Healthcare of Andover, Mass. In such embodiments, the extracorporeal system  14  may further comprise a cooler/heater for cooling or warming the heat exchange liquid, a pump for pumping that heat exchange liquid through the catheter  16 , at least one temperature sensor  24  for sensing a body temperature of the subject, a user interface  25  by which a user may enter a desired target temperature and a controller, such as a computer or microprocessor, which receives the input target temperature, the sensed body temperature and, in response, controls the temperature and/or flow rate of the heat exchange liquid to attain and maintain the input target temperature. The slurry-delivering capacity may be integrated with the heat exchange fluid controlling/delivering capacity to achieve rapid initial cooling of a subject&#39;s body using the heat exchange slurry followed by maintenance of a desired target body temperature and eventual re-warming to normothermia using the traditional heat exchange liquid (e.g., saline solution). Specific examples of such systems are shown in  FIGS. 2-7  and described herebelow. In the embodiments of  FIGS. 2-4 , a slurry concentrate is mixed with circulating heat exchange fluid to provide a slurry feed of suitable viscosity and having suitable solids content to be pumped through the particular catheter in use and to provide the desired amount of endovascular cooling. In the embodiments of 5 and 6 an in-line freezer device is used to form ice particles in the circulating heat exchange fluid.  FIG. 7  shows an alternative catheter type that may be used in conjunction with any of the extracorporeal systems shown in  FIGS. 1-6 . 
     Examples of Endovascular Temperature Management Systems Equipped to Utilize Heat Exchange Slurry for Rapid Cooling of All or Part of a Subject&#39;s Body 
       FIG. 2  shows one example of an endovascular temperature management system  10   a  of the present invention. In this particular example, the heat exchange catheter  12  comprises an elongate catheter body  16  having a heat exchanger  88  mounted on a distal portion of the catheter body  12 . As shown in the cross sections of  FIGS. 2A-2C , a proximal portion  16   a  of the catheter body comprises a flexible shaft having an inflow lumen  70 , an outflow lumen  72  and a proximal working lumen segment  74   a.  A mid-portion  16   b  of the catheter body comprises a flexible shaft having shaft having the inflow lumen  70  and working lumen  74 . A distal portion  16   c  of the catheter body has only the working lumen  74  passing therethrough. At or near the distal end of a proximal portion  16   a  of the catheter body, the outflow lumen  72  terminates and communicates through openings into the proximal ends of the three generally cylindrical balloon lobes  76   a,    76   b  and  76   c.  At or near the distal end of the mid-portion  16   b  of the catheter body, the inflow lumen  70  terminates and communicates with the distal ends of the three generally cylindrical balloon lobes  76   a ,  76   b  and  76   c.  The balloon lobes  76   a,    76   b  and  76   c  are helically twisted, wound or otherwise helically disposed about the mid-portion  16   b  of the catheter body. In this example, the mid-portion  16   b  of the catheter body comprises a continuation or extension of the inflow lumen  70  with a smaller tube connected to and forming an extension of the working lumen  74 . The attachment of the balloon lobes to the catheter may be accomplished in any appropriate manner to accomplish the circulation of heat exchange fluid described here. One such method is described in detail in U.S. Pat. No. 6,610,083 (Keller, et al.), which patent is expressly incorporated herein by reference. The distal portion  16   c  of the catheter body extends beyond the distal ends of the balloon lobes  76   a,    76   b  and  76   c.  The tube forming the mid-region extension of the working lumen  74  continues through this distal portion  16   c  of the catheter body and its lumen opens through an aperture in the distal tip of the catheter  12 . Thus, in this manner, a continuous working lumen that extends through the entire length of the heat exchange catheter  12 . However, it is to be appreciated that as an alternative, in some embodiments, a working lumen that runs less than the entire length of the catheter may be provided to facilitate rapid exchange of guidewires and/or catheters. 
     As those of skill in the art will appreciate, the working lumen  74  may facilitate advancement of the catheter  12  over a guidewire and/or to facilitate infusion of fluids (e.g., saline solution, therapeutic or diagnostic substances, radiographic contrast medium, aqueous oxygen, etc.) and/or to facilitate introduction of another catheter or apparatus into the subject&#39;s body. One example of another apparatus that may be advanced through the working lumen  74  is an endovascular embodiment of the body temperature measuring apparatus  24  (e.g., a catheter or wire having a temperature sensor that is advanceable out of the distal tip of the catheter  12  and useable for sensing the temperature of the subject&#39;s flowing blood). One example of an endovascular body temperature measuring apparatus that may be advanced through working lumen  74  is the Reprieve® endovascular temperature probe manufactured by ZOLL Circulation, Inc., Sunnyvale, Calif. 
     In typical operation when the catheter  12  is inserted via a femoral vein and the heat exchanger  18  is positioned within the inferior vena cava IVC (as shown in  FIG. 1 ), the heat exchange medium (slurry or liquid) will flow distally through the inflow lumen  70 , enter the distal ends of the balloon lobes  76   a,    76   b,    76   c,  flows in the proximal through the balloon lobes  76   a,    76   b,    76   c,  exit the proximal ends of the balloon lobes  76   a,    76   b,    76   c  into the outflow lumen  72  and then flow proximally trough the outflow lumen and out of the proximal end of the catheter  12 . 
     In this system  10   a,  the extracorporeal components comprises an extracorporeal heat exchanger  32 , a heater/cooler device  34  an air separator  52  and a a vessel  50  which contains a concentrated slurry. An outflow tube  20  connects the outflow lumen  72  the catheter  12  to an inner tube  40  of the heat exchanger  32 . A temperature sensor  36  may optionally be provided to sense the temperature of heat exchange fluid returning from the catheter  12  before it enters the extracorporeal heat exchanger  32 . Tubes  42  and  48  connect the heater/cooler device  34  to the shell  38  of the extracorporeal heat exchanger  32  to circulate fluid of a desired temperature through the shell  38 . The outlet end of the heat exchanger tube  40  is connected to air separator  52  by way of tube  21 . Thus, heat exchange fluid that returns from the catheter is passed through the heat exchanger tube  40  where its temperature is adjusted as desired and then into air separator  52 . Air removed by the air separator is vented through tube  58  into the slurry-containing vessel  50  or alternatively into the atmosphere. Liquid (with any entrained ice particles) travels from the air separator  52 , through tube  64  to pump  56 . Slurry travels from the slurry containing vessel  50  through tube  60  to pump  54 . Pumps  54  and  56  are operated to pump the desired ratio of slurry concentrate and liquid through lines  62  and  66 , respectively so that they become combined in inflow line  22 . This forms the desired heat exchange slurry which is delivered through inflow line  22 , into inflow lumen  70  of the catheter  12  such that it circulates through the catheter  12  in the above-described manner. After all or part of the subject&#39;s body has been cooled to the desired hypothermic temperature, the slurry pump  54  may be turned off and the system will continue to operate in maintenance mode using only liquid heat exchange medium without solid ice particles. 
     The slurry pump  54  will be of a type that is capable of reproducibly pumping a metered volume of the relatively thick slurry concentrate. One example of such a pump is shown schematically in  FIGS. 2D and 2E . In this non-limiting example, the pump comprises a collapsible dome diaphragm  82 , an upstream check valve  84  located upstream of the dome diaphragm  82  and a downstream check valve  86  located downstream of the dome diaphragm  82 . The check vales  84 ,  86  may be any suitable type(s) of check valves, including but not necessarily limited to ball check vales, diaphragm check valves, swing check valves, tilting disc check valves, stop check valves, lift check valves, clapper check valves, wafer check valves, duckbill check valves, electrically actuated check valves, etc. The upstream check valve  84  opens, the downstream check valve  86  closes and the dome diaphragm  82  assumes a non-compressed shape when the ram  88  cycles to its retracted position shown in  FIG. 2D . This causes slurry to flow through the upstream check valve  84  into the inner cavity of the dome diaphragm  82 . Then, when the ram  88  cycles to its advanced position as shown in  FIG. 2E , the upstream check valve  84  closes, the downstream check valve  86  opens and the dome diaphragm  82  becomes compressed, thereby expelling slurry that has accumulated within the interior of the dome diaphragm  82  through the downstream check valve  86 . In this manner, reciprocating motion of the ram  88  causes slurry to be pumped through the circuit. In the particular non-limiting example shown, each check valve  84 ,  86  comprises a rigid housing  84   a,    86   a  which defines a flow chamber therewithin, a moveable diaphragm  84   c,    86   c  and a seal ring  84   b,    86   b  located on the inner wall of the housing on the upstream side of each diaphragm  84   c,    86   c.  As shown, when the ram  88  is retracted and the dome diaphragm moves to its non-collapsed configuration, the valve diaphragms  84   c  and  86   c  are drawn inwardly, causing the upstream diaphragm  84   c  to separate away from the adjacent seal ring  84   b  (thereby opening the upstream check valve  84 ) and causing the downstream valve diaphragm  86   c  to seat firmly against the adjacent seal ring  86   b  (thereby closing the downstream check valve  86  to close. The speed at which the ram member  88  reciprocates will dictate the slurry concentrate throughput rate of this pump  54 . 
       FIG. 3  shows another example of an endovascular temperature management system  10   b  of the present invention. In this example, the system  10   b  incorporates a catheter  12 , extracorporeal heat exchanger  32  and heater cooler  34  and interconnecting conduits  20 ,  22 ,  42 ,  48  of the same type as described above with respect to  FIG. 2 . However, this system  10   b  differs from the showing of  FIG. 2  in that portion B of this system  10   b  replaces portion A of the system  10   a  seen in  FIG. 2 . 
     Portion B of system  10   b  combines a slurry concentrate with a diluent fluid (e.g., heat exchange fluid that has returned from the catheter  12 ) to form a heat exchange slurry that is then circulated through the catheter  12 . As shown, the outlet end of the extracorporeal heat exchanger tube  40  is connected to air separator  52  by way of tube  21 . Heat exchange medium returning from the catheter  12  (with or without any remaining frozen particles) passes through the heat exchanger tube  40  where its temperature may be adjusted as desired and then into air separator  52 . Air removed by the air separator  52  is vented through tube  58 . The remaining heat exchange liquid (with any remaining ice particles that did not melt during the prior circulation through the circuit) is pumped by pump  56  through line  64  and into line  66 . The slurry concentrate injector  90  comprises a housing  94  having an enclosed inner cavity  95  that contains a slurry concentrate, a piston  96  which is in substantially sealing contact with the inner wall of the cavity  95  and a drive  98  for driving the piston  96 . As the drive  98  advances the piston  96 , the piston  96  forces slurry concentrate out of the injector&#39;s inner cavity  95  through line  92 . The piston drive  95  may be manual, machine-driven, hydraulic, gas-driven or may be driven in any other suitable manner that causes the piston  96  to advance at a desired rate or rates to thereby deliver desired ratio(s) of slurry concentrate to be combined with the circulating heat exchange liquid. Line  92  joins with line  66  such that the heat exchange liquid flowing through line  66  combines with slurry concentrate flowing though line  92 , thereby creating heat exchange slurry of a desired consistency in inflow line  22 . This heat exchange slurry then flows through inflow line  22  and circulates through the catheter  12  in the manner described above. 
       FIG. 4  shows another example of an endovascular temperature management system  10   b  of the present invention. In this example, the system  10   c  incorporates a catheter  12 , extracorporeal heat exchanger  32 , a heater/cooler  34  and interconnecting conduits  20 ,  22 ,  42 ,  48  of the same type as described above with respect to  FIG. 2 . However, this system  10   c  differs from the showing of  FIG. 2  in that portion C of this system  10   c  replaces portion A of the system  10   a  seen in  FIG. 2 . 
     Portion C of system  10   c  uses a pressure driven piston system to combine a slurry concentrate with a circulating heat exchange medium (e.g., heat exchange medium that has circulated through and returned from the catheter  12 ) to form a desired heat exchange slurry that is then circulated through the inflow line  22  and into the catheter  12 . As shown, pump  56  pumps chilled heat exchange medium (with or without any remaining frozen particles) saline through the heat exchanger outlet line  21  into air separator  52 . Air removed by the air separator  52  (and potentially a quantity of overflow heat exchange medium) is vented through a vent tube  102  into a slurry concentrate injector  100  on the left side of the piston  106 . The remaining heat exchange liquid (with any remaining ice particles that did not melt during the prior circulation through the circuit) flows through line  64  and through flow restrictor  66 . The flow restrictor  66  may be adjustable to control the amount of back pressure in line  64  and the amount of overflow heat exchange medium that flows through vent tube  102  and into the slurry concentrate injector  100  on the left side of the piston  106 . The slurry concentrate injector  100  comprises a housing  102  having an enclosed inner cavity  104  that contains a slurry concentrate on the right side of piston  106 . The piston  106  is in substantially sealing slidable contact with the inner wall of the cavity  104 . As air and overflow heat exchange medium passing through vent line  102  accumulates on the left side of the piston  106  the pressure P 1  on the left side of the piston will rise. When the pressure P 1  on the left side of the piston  106  exceeds the pressure P 2  on the right side of the piston  106 , the piston  106  will advance as indicated by arrows on  FIG. 4 . Such advancement of the piston  106  in response to the incoming air forces slurry concentrate out of the injector&#39;s inner cavity  104  through line  105 . Line  105  joins with line  64  such that the heat exchange liquid flowing through line  64  combines with slurry concentrate flowing though line  104 , thereby creating heat exchange slurry of a desired consistency in inflow line  22 . This heat exchange slurry then flows through inflow line  22  and circulates through the catheter  12  in the manner described above. The amount of flow restriction caused by the flow restrictor  66  may be adjusted to result in the desired heat exchange slurry consistency (i.e., the desired ratio of ice particles to liquid). In this or any embodiments of the present invention, an automated microprocessor, computer or other controller may receive signals from a sensor (see  FIGS. 9A and 9B ) which senses the consistency of the heat exchange slurry flowing through inflow line  22 . In response, such microprocessor, computer or other controller may issue control signals to other components of the system to change the relative amounts of ice particles and liquid in that heat exchange slurry. In this particular embodiment, such microprocessor, computer or other controller may be programmed to issue control signals to the flow restrictor  66  to adjust the amount of flow allowed through the flow restrictor  66  in a manner that results in the desired heat exchange slurry consistency in line  22  (i.e., the desired ratio of ice particles to liquid). 
       FIG. 5  shows another example of an endovascular temperature management system  10   d  of the present invention. In this example, the system  10   d  incorporates a catheter  12 , extracorporeal heat exchanger  32  and heater cooler  34  and interconnecting conduits  20 ,  22 ,  42 ,  48  of the same type as described above with respect to  FIG. 2 . However, this system  10   d  differs from the showing of  FIG. 2  in that portion D of this system  10   d  replaces portion A of the system  10   a  seen in  FIG. 2 . In this system  10   d,  no slurry is required to be prepared offline. Instead, a fluid source, such as a bag of liquid saline  114 , is spiked or otherwise connected to the system  10   d  and a freezer device, such as a disposable slurry generator  120 , is used to form a desired amount of frozen solid matter in the circulating heat exchange liquid. In the embodiment shown, the outlet end of the extracorporeal heat exchanger tube  40  is connected to an air separator  112  by way of tube  21 . Heat exchange medium returning from the catheter  12  (with or without any remaining frozen particles) passes through the heat exchanger tube  40  where its temperature may be adjusted as desired and then into air separator  112 . Air removed by the air separator  112  is vented through tube a hydrophobic membrane  118 . Additional heat exchange liquid (e.g., saline solution) from bag  114  passes through line  116  and into air separator  112  to combine with the remaining liquid and to make up for the volume of gas that has been vented through hydrophobic membrane  118 . The heat exchange liquid (with any remaining ice particles that did not melt during the prior circulation through the circuit) is pumped by pump  56  through lines  64  and  66  and into slurry generator  120 . It is to be appreciated, however, that the extracorporeal heat exchanger  32  and heater/cooler  34  are optional components of this system. If such optional components were eliminated from the system, the heat exchange medium returning from the catheter  12  via return line  20  would flow directly into line  21  and into the air separator  112 . 
       FIGS. 5A and 5B  show additional details of the slurry generator  120  used in this example. The slurry generator  120  comprises an enclosed generally cylindrical vessel  122  having a sealed rotating shaft  130  extending thereinto. A generally round scraper  126  is attached to the shaft  130 . The rotation of the shaft may be driven by a variable speed electric motor  132  or any other suitable means. Chiller(s), such as refrigerated block members  128   a,    128   b  having refrigeration coils  136  therein, are positioned adjacent to the vessel  122  to cool the walls of the vessel  122  to a temperature which causes the heat exchange liquid to freeze when it contacts the inner wall of the vessel  122 . The refrigerated block members  128   a,    128   b  may be reuseable and the vessel  122 , shaft  130  and scraper  124  may be disposable. The refrigerated block members  128   a,    128   b  may be moveable away from each other to allow removal and replacement of the disposable vessel  122 /shaft  130 /scraper  124  unit and then the refrigerated block members  128   a,    128   b  may be moveable back toward each other to surround or abut the outer surface of the vessel  122 , thereby providing for efficient heat exchange between the refrigerated block members  128   a ,  128   b  and the wall of the vessel  122 . During operation, the rotating scraper  124  separates formed particles of frozen matter from the vessel wall, causing such particles of frozen matter to become combined with unfrozen liquid (and any residual frozen particles that did not melt during a prior circulation through the catheter  12 ) flowing through the vessel  122 . This forms the desired heat exchange slurry having the desired ratio of frozen solid particles to liquid. This heat exchange slurry then exits the vessel  122  and flows through inflow line  22  and circulates through the catheter  12  in the manner described above. 
     The rate of ice formation in the slurry generator  120  may be controlled by adjusting the amount of cooling applied to the wall of the vessel  122  and/or the speed of the scraper  124 . Temperature feedback may be used to adjust the rate of ice formation to optimize the saline return temperature and, possibly, to ensure that the amount of any ice particles remaining in the recirculated heat exchange medium is not more than can be suitably pumped by the pump  56 . To facilitate this, or more temperature sensor(s)  138  may optionally be provided to sense the temperature of the refrigerated block members  128   a,    128   b  and/or the temperature of the wall of the vessel  122 . A controller may be programmed to receive the temperature(s) sensed by such temperature sensor(s) and to modify, in response, the temperature of the vessel  122  and/or the flow rate of heat exchange fluid delivered by the pump  56  and/or the rate of rotation of the scraper  124 , as needed, to control the amount of frozen solid phase matter in the heat exchange slurry. 
       FIG. 6  shows another example of an endovascular temperature management system  10   e  of the present invention. In this example, the system  10   e  incorporates a catheter  12  and interconnecting conduits  20 ,  22  of the same type as described above with respect to  FIG. 2 . However, this system  10   e  differs from the showing of  FIG. 2  in that portion E of this system  10   e  replaces portion A of the system  10   a  seen in  FIG. 2  and the extracorporeal heat exchanger  32  and heater cooler  34  and interconnecting conduits  42 ,  48  are not present, but may optionally be included. In this system  10   e,  no slurry is required to be prepared offline. A reservoir  180 , such as a bag of liquid saline solution  180  or other container, is connected to the return line  20  which returns heat exchange medium from the catheter (including any particles of frozen solid phase matter that did not melt while circulating through the catheter  12 ) and to an outlet line  56 . The returning heat exchange medium (including any residual frozen solid phase matter) flows from return line  20  and into reservoir  180 , where it combines with any heat exchange medium that is already present in the reservoir  180 . In some embodiments, the reservoir  180  may be compliant or may include an air vent to allow separation of air for the liquid (and any residual solid phase matter). Heat exchange medium then flows out of the reservoir  180  through line  182 , through pump  56 , through line  184  and into slurry generator  186 , where a portion of the liquid phase becomes frozen to form a heat exchange slurry of a desired solid/liquid consistency. 
     In the system  10   d  of  FIG. 6 , the slurry generator  186  comprises an enclosed generally frustoconical vessel  188  having a sealed rotating shaft  190  extending thereinto. A generally round scraper  191  of tapered diameter is attached to the shaft  190 . The rotation of the shaft  188  may be driven by a variable speed electric motor (not shown) or any other suitable means. Chiller(s), such as one or more refrigerated block member(s)  192   a,    192   b,  define a tapered cavity  193 . The vessel  188 , with its shaft  191  and scraper  190  positioned therein, is insertable in the tapered cavity  193 , without necessarily requiring movement of the refrigerated block member(s)  192   a,    192   b . When the vessel  188  is positioned within the tapered cavity  193 , the wall of the vessel will be in abutment with or in heat exchange proximity to the refrigerated block member(s)  192   a,    192   b.  In this manner, the refrigerated block member(s)  192   a,    192   b  will cool the wall of the vessel  188 . During operation, the rotating scraper  191  separates formed particles of frozen matter from the wall of the vessel  188 , causing such particles of frozen matter to become combined with unfrozen liquid flowing through the vessel  188 . This forms the desired heat exchange slurry having the desired ratio of frozen solid particles to liquid. This heat exchange slurry then exits the vessel  188  through line  194 . Line  194  is connected to the inflow line  20  through which the slurry then flows into, and circulates through, the catheter  12  in the above-described manner. 
     As in other embodiments, the rate of ice formation in this slurry generator  186  may be controlled by adjusting the amount of cooling applied to the wall of the vessel  188  and/or the speed of the scraper  191 . Temperature feedback may be used to adjust the rate of ice formation to optimize the saline return temperature and, possibly, to ensure that the amount of any ice particles remaining in the recirculated heat exchange medium is not more than can be suitably pumped by the pump  56 . To facilitate this, or more temperature sensor(s) (not shown in  FIG. 6 ) may optionally be provided ate one or more location(s) in the system  10   e  to sense the temperature of the refrigerated block members  128   a,    128   b  and/or the temperature of the wall of the vessel  122  and/or the temperature of the heat exchange medium. A controller may be programmed to receive the temperature(s) sensed by such temperature sensor(s) and to modify, in response, the temperature of the vessel  188  and/or the flow rate of heat exchange fluid delivered by the pump  56  and/or the rate of rotation of the scraper  124 , as needed, to control the amount of frozen solid phase matter in the heat exchange slurry. 
     It is to be appreciated that, the catheter through which the heat exchange slurry is circulated need not be the specific catheter  12  shown and described in the above-set-forth examples, but rather, may be any suitable catheter by which heat exchange may occur between the heat exchange slurry and the subject&#39;s body or flowing blood without causing the slurry to directly contact or mix with any body fluid or tissue of the subject&#39;s body. Some catheters may be capable of use with more concentrated slurries than others because of limitations in the size or configuration of the catheter lumen(s) or other aspects of the catheter construction. Also, the heat exchange slurry need not necessarily circulate in and out of the same end of the catheter. Rather, as shown in  FIG. 7 , in some embodiments the proximal and distal ends PE, DE of the catheter  12   a  may both be exteriorized while a portion of the catheter between the ends PE, DE extends through the subject&#39;s vasculature or body. In this manner, the heat exchange slurry may enter one end DE or PE of the catheter  12   a  and may exit the other end De, PE. Examples of various heat exchange catheters that may be used in connection with this invention include those commercially available from ZOLL Circulation, Inc. of Sunnyvale, Calif. and Koninklijke Philips Electronics N.V./Phillips Healthcare (InnerCool), Andover, Mass. 
     The air separators  52  or  112  used in systems of the present invention may comprise any suitable types of air separating devices capable of removing bubbles or entrained air from liquid (and any sold or ice particles that may be present with the liquid as it passes through the air separator.  FIG. 8  shows a non-limiting example of one type of air separator  52   a  that may be used. This air separator  52   a  comprises a housing  200  which defines an inner chamber  206  having an inlet port  202  and an outlet port  204 . An air permeable member  208  (e.g., a filter) or open vent is located at the top of the housing. Heat exchange medium or slurry flows through inlet port  204  and pools in or flows through the inner chamber  204 , where entrained air will rise to the top of the chamber  206  and escape through the air permeable member  208  or open vent. The remaining liquid or slurry will flow out of the outlet port  204 . In some embodiments, the air will simply vent into the environment. In other embodiments, where indicated, a vent tube or other conduit may be attached to the opening at the top of the housing  200  so that air which flows outwardly though the air permeable member  208  or open vent will be channeled through that vent tube or conduit to a desired location (see for example the embodiment of  FIG. 4  where air from the air separator  52  is channeled through a vent tube  102  and used to drive a piston of an injector device  100 . 
       FIGS. 9A and 9B  show sensors that may be used at various locations in any system of the present invention to sense the presence or absence of heat exchange medium and/or to sense the relative amounts of solid phase and liquid phase matter in slurry being circulated through the system Specifically,  FIG. 9A  shows a level sensor  210  of a type known in the art, which may be used to sense the level of heat exchange fluid in any tank, vessel, cassette, heat exchanger or other collection chamber of the system. In this sensor  210 , light leaves an emitter/detector  214  located underneath a prism that may be molded into the wall  216  of the tank, vessel, cassette, heat exchanger or other collection chamber. If the tank, vessel, cassette, heat exchanger or other collection chamber is full of liquid, light transmits through the prism (refracting slightly) along path A, reflects off of a mirror, and travels back down through the prism where it is received by the detector element of the emitter/detector  214 . If the tank, vessel, cassette, heat exchanger or other collection chamber reservoir is empty, light reflects off of the 45 degree angled surface  212  of the prism along path B, thereby causing the light to be scattered around the tank, vessel, cassette, heat exchanger or other collection chamber such that substantially no light returns to the detector element of the emitter/detector  214 . If the reservoir contains liquid/ice slurry, light will reflect off of the ice particles, resulting in a moderate level of transmittance to the detector element of the emitter/detector  214 . 
       FIG. 9B  shows a sensor  218  that comprises a clamp  220  (off the shelf or custom) which goes around the outer diameter of a clear tube  222 . Infrared light leaves an emitter  224  and enters the clear tube wall. If the tube is full of saline/water/liquid, the light transmits straight through the tube and on to the detector  226 . If the tube contains air, some of the light will reflect off the tube wall, resulting in a low level of transmittance to the detector. If the tube contains a liquid/ice slurry, some of the light will reflect off of the ice particles, resulting in a moderate level of transmittance to the detector. Thus, one or more of these sensors  218  may be used to sense the amount of solid phase matter (e.g., ice) present in heat exchange fluid flowing through one or more tubes of the system. 
     The amount of solid phase matter in the heat exchange slurry may vary depending on the lumen size(s), heat exchanger configurations and flow restrictions inherent in design of the particular heat exchange catheter being used. Table 1 below shows examples of slurry concentrations, flow rates and resultant rates of solid phase matter delivery for several commercially available heat exchange catheters: 
     
       
         
           
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                   
                 Flow Rate of 
                 Concentration of 
                 Resultant Rate 
               
               
                 Commercially 
                 Heat Exchange 
                 Solid Phase 
                 of Delivery of 
               
               
                 Available 
                 Medium 
                 Matter (e.g., 
                 Solid Phase 
               
               
                 Catheter 
                 Through 
                 Ice) in Heat 
                 Matter (e.g., 
               
               
                 Example 
                 Catheter 
                 Exchange Slurry 
                 Ice) 
               
               
                   
               
             
            
               
                 Quattro ® (ZOLL 
                 200 mL/min 
                 50% 
                 100 g/min 
               
               
                 Circulation, 
               
               
                 Sunnyvale, CA) 
               
               
                 Radiant GTO ® 
                 900 mL/min 
                 11% 
                 100 g/min 
               
               
                 (ZOLL Circulation, 
               
               
                 Sunnyvale, CA) 
               
               
                 Solex/ICY ® 
                 200 mL/min 
                 18% 
                  35 g/min 
               
               
                 (ZOLL Circulation, 
               
               
                 Sunnyvale, CA) 
               
               
                   
               
            
           
         
       
     
     Thus, for these particular heat exchange catheters, the concentration of solid phase matter within the heat exchange slurry may range from about 18% by weight to about 50% by weight and the flow rate of the heat exchange slurry through the catheter may vary from about 200 mL/min (for relatively small catheters) to about 900 mL/min (for a relatively large catheter). 
     Although the examples shown in the drawings and described above are specific to heat exchange catheters wherein the at least a portion of the solid phase matter melts as it circulates through the catheter, it is to be appreciated that the invention is also useable in connection with body cooling devices other than catheters (e.g., cooling blankets, pads and other surface cooling devices through which a heat exchange medium is circulated. Also, it is to be appreciated that the solid phase matter need not necessarily melt while it is within the catheter or other body cooling device. Indeed, the melting of solid phase matter anywhere within the heat exchange medium flow path—even in an extracorporeal portion of the flow path—will enhance the removal of heat from the heat exchange medium. The energy transfer (Q) through the heat exchanger is dependent on three factors:
         1) the heat transfer coefficient (h) of the exchanger,   2) the amount of surface area (A) available for heat transfer, and   3) the difference in temperature (ΔT) between the heat exchange medium circulating through the heat exchanger and the blood or other body fluid circulating through the subject&#39;s body in heat exchange proximity to the heat exchanger.       

     This may be mathematically expressed as follows: 
     
       
      
       Q=h*A*ΔT  
      
     
     Increasing the efficiency or size of the heat exchanger (h and A), generally speaking, requires increasing the cost of the heat exchanger. In embodiments where the heat exchanger is part of a sterile, disposable catheter intended for disposal after a single use, substantial increases in cost may be undesirable. Therefore, the present invention provides a more cost-effective means of increasing energy transfer through the heat exchanger by effecting a solid to liquid phase change within the heat exchange medium, thereby enhancing the removal of heat from the heat exchange medium and resulting in a greater ΔT. To effect this solid to liquid phase change, solid phase matter must be created or introduced in the heat exchange medium in a manner that does not result in clogging or fowling of the system. The examples described above avoid problems of ice clogging or fowling flow. For example, in embodiments which employ a slurry-generating device or slurry source within the extracorporeal portion of the heat exchange fluid recirculation flow path, ice particles are introduced into the flowing heat exchange fluid and at least some of those ice particles subsequently melt somewhere downstream of the location at which they were introduced. In this way, ice particles act as a heat transport mechanism, effectively increasing the surface area of the cold source and subsequently undergoing a solid to liquid phase change. This achieves greater heat transfer and more efficient and rapid cooling of the subject&#39;s body than traditional heat exchange catheter systems circulating liquid phase heat exchange fluid which cannot have an initial temperature less than 0 C. 
     The invention has been described hereabove with reference to certain examples or embodiments of the invention. No attempt has been made to exhaustively describe all possible embodiments and examples of the invention. Indeed, various additions, deletions, alterations and modifications may be made to the above described examples and embodiments without departing from the intended spirit and scope of the invention. For example, any element or attribute of one embodiment or example may be incorporated into or used with another embodiment or example, unless to do so would render the embodiment or example unsuitable for its intended use. Also, where the steps of a method or process are described, listed or claimed in a particular order, such steps may be performed in any other order unless to do so would render the embodiment or example un-novel, obvious to a person of ordinary skill in the relevant art or unsuitable for its intended use. All reasonable additions, deletions, modifications and alterations are to be considered equivalents of the described examples and embodiments and are to be included within the scope of the following claims.