Abstract:
A method and apparatus for performing hypothermia of a selected organ without significant effect on surrounding organs or other tissues. A flexible catheter is inserted through the vascular system of a patient to place the distal tip of the catheter in an artery feeding the selected organ. A compressed refrigerant is pumped through the catheter to an expansion element near the distal tip of the catheter, where the refrigerant vaporizes and expands to cool a flexible heat transfer element in the distal tip of the catheter. The heat transfer element cools the blood flowing through the artery, to cool the selected organ, distal to the tip of the catheter.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
       [0001]    This application is a continuation application of co-pending U.S. application Ser. No. 09/834,054, filed Apr. 12, 2001, titled “Selective Organ Hypothermia Method and Apparatus”, which is a continuation application of U.S. application Ser. No. 09/650,940, filed Aug. 30, 2000, titled “Selective Organ Hypothermia Method and Apparatus”, now U.S. Pat. No. 6,482,226, which is a continuation of U.S. application Ser. No. 09/306,866, filed May 07, 1999, titled “Selective Organ Hypothermia Method and Apparatus”, now U.S. Pat. No. 6,235,048, which is a divisional application of U.S. application Ser. No. 09/012,287, filed Jan. 23, 1998, titled “Selective Organ Hypothermia Method and Apparatus”, now U.S. Pat. No. 6,051,019. 
     
    
     
       STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT  
         [0002]    Not Applicable  
         BACKGROUND OF THE INVENTION  
         [0003]    1. Field of the Invention  
           [0004]    The current invention relates to selective cooling, or hypothermia, of an organ, such as the brain, by cooling the blood flowing into the organ. This cooling can protect the tissue from injury caused by anoxia or trauma.  
           [0005]    2. Background Information  
           [0006]    Organs of the human body, such as the brain, kidney, and heart, are maintained at a constant temperature of approximately 37° C. Cooling of organs below 35° C. is known to provide cellular protection from anoxic damage caused by a disruption of blood supply, or by trauma. Cooling can also reduce swelling associated with these injuries.  
           [0007]    Hypothermia is currently utilized in medicine and is sometimes performed to protect the brain from injury. Cooling of the brain is generally accomplished through whole body cooling to create a condition of total body hypothermia in the range of 20° to 30° C. This cooling is accomplished by immersing the patient in ice, by using cooling blankets, or by cooling the blood flowing externally through a cardiopulmonary bypass machine. U.S. Pat. No. 3,425,419 to Dato and U.S. Pat. No. 5,486,208 to Ginsburg disclose catheters for cooling the blood to create total body hypothermia However, they rely on circulating a cold fluid to produce cooling. This is unsuitable for selective organ hypothermia, because cooling of the entire catheter by the cold fluid on its way to the organ would ultimately result in non-selective, or total body, cooling.  
           [0008]    Total body hypothermia to provide organ protection has a number of drawbacks. First, it creates cardiovascular problems, such as cardiac arrhythmias, reduced cardiac output, and increased systemic vascular resistance. These side effects can result in organ damage. These side effects are believed to be caused reflexively in response to the reduction in core body temperature. Second, total body hypothermia is difficult to administer. Immersing a patient in ice water clearly has its associated problems. Placement on cardiopulmonary bypass requires surgical intervention and specialists to operate the machine, and it is associated with a number of complications including bleeding and volume overload. Third, the time required to reduce the body temperature and the organ temperature is prolonged. Minimizing the time between injury and the onset of cooling has been shown to produce better clinical outcomes.  
           [0009]    Some physicians have immersed the patient&#39;s head in ice to provide brain cooling. There are also cooling helmets, or head gear, to perform the same. This approach suffers from the problems of slow cool down and poor temperature control due to the temperature gradient that must be established externally to internally. It has also been shown that complications associated with total body cooling, such as arrhythmia and decreased cardiac output, can also be caused by cooling of the face and head only.  
           [0010]    Selective organ hypothermia has been studied by Schwartz, et. al. Utilizing baboons, blood was circulated and cooled externally from the body via the femoral artery and returned to the body through the carotid artery. This study showed that the brain could be selectively cooled to temperatures of 20° C. without reducing the temperature of the entire body. Subsequently, cardiovascular complications associated total body hypothermia did not occur. However, external circulation of the blood for cooling is not a practical approach for the treatment of humans. The risks of infection, bleeding, and fluid imbalance are great. Also, at least two arterial vessels must be punctured and cannulated. Further, percutaneous cannulation of the carotid artery is very difficult and potentially fatal, due to the associated arterial wall trauma. Also, this method could not be used to cool organs such as the kidneys, where the renal arteries cannot be directly cannulated percutaneously.  
           [0011]    Selective organ hypothermia has also been attempted by perfusing the organ with a cold solution, such as saline or perflourocarbons. This is commonly done to protect the heart during heart surgery and is referred to as cardioplegia. This procedure has a number of drawbacks, including limited time of administration due to excessive volume accumulation, cost and inconvenience of maintaining the perfusate, and lack of effectiveness due to temperature dilution from the blood. Temperature dilution by the blood is a particular problem in high blood flow organs such as the brain. For cardioplegia, the blood flow to the heart is minimized, and therefore this effect is minimized.  
           [0012]    Intravascular, selective organ hypothermia, created by cooling the blood flowing into the organ, is the ideal method. First, because only the target organ is cooled, complications associated with total body hypothermia are avoided. Second, because the blood is cooled intravascularly, or in situ, problems associated with external circulation of blood are eliminated. Third, only a single puncture and arterial vessel cannulation is required, and it can be performed at an easily accessible artery such as the femoral, subclavian, or brachial. Fourth, cold perfusate solutions are not required, thus eliminating problems with excessive fluid accumulation. This also eliminates the time, cost, and handling issues associated with providing and maintaining cold perfusate solution. Fifth, rapid cooling can be achieved. Sixth, precise temperature control is possible.  
           [0013]    Previous inventors have disclosed the circulation of a cold fluid to produce total body hypothermia, by placing a probe into a major vessel of the body. This approach is entirely unfeasible when considering selective organ hypothermia, as will be demonstrated below.  
           [0014]    The important factor related to catheter development for selective organ hypothermia is the small size of the typical feeding artery, and the need to prevent a significant reduction in blood flow when the catheter is placed in the artery. A significant reduction in blood flow would result in ischemic organ damage. While the diameter of the major vessels of the body, such as the vena cava and aorta, are as large as 15 to 20 mm., the diameter of the feeding artery of an organ is typically only 4.0 to 8.0 mm. Thus, a catheter residing in one of these arteries cannot be much larger than 2.0 to 3.0 mm. in outside diameter. It is not practical to construct a selective organ hypothermia catheter of this small size using the circulation of cold water or other fluid. Using the brain as an example, this point will be illustrated.  
           [0015]    The brain typically has a blood flow rate of approximately 500 to 750 cc/min. Two carotid arteries feed this blood supply to the brain. The internal carotid is a small diameter artery that branches off of the common carotid near the angle of the jaw. To cool the brain, it is important to place some of the cooling portion of the catheter into the internal carotid artery, so as to minimize cooling of the face via the external carotid, since face cooling can result in complications, as discussed above. It would be desirable to cool the blood in this artery down to 32° C., to achieve the desired cooling of the brain. To cool the blood in this artery by a 5° C. drop, from 37° C. down to 32° C., requires between 100 and 150 watts of refrigeration power.  
           [0016]    In order to reach the internal carotid artery from a femoral insertion point, an overall catheter length of approximately 100 cm. would be required. To avoid undue blockage of the blood flow, the outside diameter of the catheter can not exceed approximately 2 mm. Assuming a coaxial construction, this limitation in diameter would dictate an internal supply tube of about 0.70 mm. diameter, with return flow being between the internal tube and the external tube.  
           [0017]    A catheter based on the circulation of water or saline operates on the principle of transferring heat from the blood to raise the temperature of the water. Rather than absorbing heat by boiling at a constant temperature like a freon, water must warm up to absorb heat and produce cooling. Water flowing at the rate of 5.0 grams/sec, at an initial temperature of 0° C. and warming up to 5° C., can absorb 100 watts of heat. Thus, the outer surface of the heat transfer element could only be maintained at 5° C., instead of 0° C. This will require the heat transfer element to have a surface area of approximately 1225 mm 2 . If a catheter of approximately 2.0 mm. diameter is assumed, the length of the heat transfer element would have to be approximately 20 cm.  
           [0018]    In actuality, because of the overall length of the catheter, the water would undoubtedly warm up before it reached the heat transfer element, and provision of 0° C. water at the heat transfer element would be impossible. Circulating a cold liquid would cause cooling along the catheter body and could result in non-specific or total body hypothermia. Furthermore, to achieve this heat transfer rate, 5 grams/sec of water flow are required. To circulate water through a 100 cm. long, 0.70 mm. diameter supply tube at this rate produces a pressure drop of more than 3000 psi. This pressure exceeds the safety levels of many flexible medical grade plastic catheters. Further, it is doubtful whether a water pump that can generate these pressures and flow rates can be placed in an operating room.  
         BRIEF SUMMARY OF THE INVENTION  
         [0019]    The selective organ cooling achieved by the present invention is accomplished by placing a cooling catheter into the feeding artery of the organ. The cooling catheter is based on the vaporization and expansion of a compressed and condensed refrigerant, such as freon. In the catheter, a shaft or body section would carry the liquid refrigerant to a distal heat transfer element where vaporization, expansion, and cooling would occur. Cooling of the catheter tip to temperatures above minus 2° C. results in cooling of the blood flowing into the organ located distally of the catheter tip, and subsequent cooling of the target organ. For example, the catheter could be placed into the internal carotid artery, to cool the brain. The size and location of this artery places significant demands on the size and flexibility of the catheter. Specifically, the outside diameter of the catheter must be minimized, so that the catheter can fit into the artery without compromising blood flow. An appropriate catheter for this application would have a flexible body of 70 to 100 cm. in length and 2.0 to 3.0 mm. in outside diameter.  
           [0020]    It is important for the catheter to be flexible in order to successfully navigate the arterial path, and this is especially true of the distal end of the catheter. So, the distal end of the catheter must have a flexible heat transfer element, which is composed of a material which conducts heat better than the remainder of the catheter. The catheter body material could be nylon or PBAX, and the heat transfer element could be made from nitinol, which would have approximately 70 to 100 times the thermal conductivity of the catheter body material, and which is also superelastic. Nitinol could also be treated to undergo a transition to another shape, such as a coil, once it is placed in the proper artery. Certain tip shapes could improve heat transfer as well as allow the long tip to reside in arteries of shorter length.  
           [0021]    The heat transfer element would require sufficient surface area to absorb 100 to 150 watts of heat. This could be accomplished with a 2 mm. diameter heat transfer tube, 15 to 18 cm. in length, with a surface temperature of 0° C. Fins can be added to increase the surface area, or to maintain the desired surface area while shortening the length.  
           [0022]    The cooling would be provided by the vaporization and expansion of a liquid refrigerant, such as a freon, across an expansion element, such as a capillary tube. For example, freon R12 boiling at 1 atmosphere and a flow rate of between 0.11 and 0.18 liter/sec could provide between approximately 100 and 150 watts of refrigeration power. Utilizing a liquid refrigerant allows the cooling to be focused at the heat transfer element, thereby eliminating cooling along the catheter body. Utilizing boiling heat transfer to the expanded fluid also lowers the fluid flow rate requirement to remove the necessary amount of heat from the blood. This is important because the required small diameter of the catheter would have higher pressure drops at higher flow rates.  
           [0023]    The catheter would be built in a coaxial construction with a 0.70 mm. inner supply tube diameter and a 2.0 mm. outer return tube diameter. This limits the pressure drops of the freon along the catheter length, as well as minimizing the catheter size to facilitate carotid placement. The inner tube would carry the liquid freon to the tubular heat transfer element at the distal end of the catheter body. If a heat transfer element surface temperature of 0° C. is maintained, just above the freezing point of blood, then 940 mm 2  of surface area in contact with the blood are required to lower the temperature of the blood by the specified 5° C. drop. This translates to a 2.0 mm. diameter heat transfer tube by 15 cm. in length. To generate 0° C. on the nitinol surface, the freon must boil at a temperature of minus 28° C. It is important to have boiling heat transfer, which has a higher heat transfer coefficient, to maintain the surface temperature at 0° C. There are several freons that can be controlled to boil at minus 28° C., such as a 50/50 mixture of pentafluoroethane and 1,1,1 trifluoroethane or a 50/50 mixture of difluoromethane and pentafluoroethane. The 50/50 mixture of pentafluoroethane and 1,1,1 trifluoroethane would require a flow rate of approximately 7.0 liters/min or 0.52 gram/sec to absorb 100 watts of heat. At this flow rate, the pressure drop along the inner tube is less than 7 psi in 100 cm. of length, and the pressure drop along the outer tube is less than 21 psi in 100 cm. of length.  
           [0024]    The inner supply tube of the catheter would be connected to a condenser, fed by the high pressure side of a compressor, and the outer return tube of the catheter would be connected to the low pressure side of the compressor.  
           [0025]    The novel features of this invention, as well as the invention itself, will be best understood from the attached drawings, taken along with the following description, in which similar reference characters refer to similar parts, and in which: 
       
    
    
     BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS  
       [0026]    [0026]FIG. 1 is a schematic, partially in section, showing a first embodiment of the flexible catheter according to the present invention;  
         [0027]    [0027]FIG. 2 is a perspective view of a second embodiment of the distal tip of the catheter of the present invention, after transformation;  
         [0028]    [0028]FIG. 3 is a section view of a third embodiment of the distal tip of the catheter of the present invention, after expansion of the heat transfer element;  
         [0029]    [0029]FIG. 4 is a partial section view of a fourth embodiment of the distal tip of the catheter of the present invention, after transformation;  
         [0030]    [0030]FIG. 5 is an elevation view of a fifth embodiment of the distal tip of the catheter of the present invention, before transformation;  
         [0031]    [0031]FIG. 6 is an elevation view of the embodiment shown in FIG. 5, after transformation to a double helix;  
         [0032]    [0032]FIG. 7 is an elevation view of the embodiment shown in FIG. 5, after transformation to a looped coil;  
         [0033]    [0033]FIG. 8 is an elevation view of a sixth embodiment of the distal tip of the catheter of the present invention, showing longitudinal fins on the heat transfer element;  
         [0034]    [0034]FIG. 9 is an end view of the embodiment shown in FIG. 8;  
         [0035]    [0035]FIG. 10 is an elevation view of a seventh embodiment of the distal tip of the catheter of the present invention, showing annular fins on the heat transfer element; and  
         [0036]    [0036]FIG. 11 is an end view of the embodiment shown in FIG. 10.  
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0037]    As shown in FIG. 1, the apparatus of the present invention includes a flexible catheter assembly  10 , fed by a refrigeration compressor unit  12 , which can include a condenser. The compressor unit  12  has an outlet  14  and an inlet  16 . The catheter assembly  10  has an outer flexible catheter body  18 , which can be made of braided PBAX or other suitable catheter material. The catheter body  18  must be flexible, to enable passage through the vascular system of the patient to the feeding artery of the selected organ. The inner lumen  19  of the catheter body  18  serves as the return flow path for the expanded refrigerant. The catheter assembly  10  also has an inner flexible refrigerant supply conduit  20 , which can be made of nylon, polyimide, nitinol, or other suitable catheter material. The length and diameter of the catheter body  18  and refrigerant supply conduit  20  are designed for the size and location of the artery in which the apparatus will be used. For use in the internal carotid artery to achieve hypothermia of the brain, the catheter body  18  and refrigerant supply conduit  20  will have a length of approximately 70 to 100 centimeters. The catheter body  18  for this application will have an outside diameter of approximately 2.5 millimeters and an inside diameter of approximately 2.0 millimeters, and the refrigerant supply conduit will have an outside diameter of approximately 1.0 millimeter and an inside diameter of approximately 0.75 millimeter. A supply conduit  20  of this diameter will have a refrigerant pressure drop of only approximately 0.042 atmospheres per 100 centimeters. The return flow path through a catheter body  18  of this diameter will have a refrigerant pressure drop of only approximately 0.064 atmospheres per 100 centimeters.  
         [0038]    The compressor outlet  14  is attached in fluid flow communication, by known means, to a proximal end of the refrigerant supply conduit  20  disposed coaxially within said catheter body  18 . The distal end of the refrigerant supply conduit  20  is attached to an expansion element, which in this embodiment is a capillary tube  22  having a lenght of approximately 15 to 25 centimeters. The capillary tube  22  can be made of polyimide or nitinol, or other suitable material, and it can be a separate element attached to the supply conduit  20 , or it can be an integral portion of the supply conduit  20 . For the internal carotid artery application, the capillary tube  22  will have an outside diameter of approximately 0.6 millimeter and an inside diameter of approximately 0.25 millimeter. The expansion element, such as the capillary tube  22 , has an outlet within a chamber of a flexible heat transfer element such as the hollow flexible tube  24 . The tube  24  shown in this embodiment is flexible but essentially straight in its unflexed state. The heat transfer element must be flexible, to enable passage through the vascular system of the patient to the feeding artery of the selected organ. For the internal carotid application the flexible tube  24  will have a length of approximately 15 centimeters, an outside diameter of approximately 1.9 millimeters and an inside diameter of approximately 1.5 millimeters. The heat transfer element also includes a plug  26  in the distal end of the flexible tube  24 . The plug  26  can be epoxy potting material, plastic, or a metal such as stainless steel or gold. A tapered transition of epoxy potting material can be provided between the catheter body  18  and the flexible tube  24 .  
         [0039]    A refrigerant, such as freon, is compressed, condensed, and pumped through the refrigerant supply conduit  20  to the expansion element, or capillary tube,  22 . The refrigerant vaporizes and expands into the interior chamber of the heat transfer element, such as the flexible tube  24 , thereby cooling the heat transfer element  24 . Blood in the feeding artery flows around the heat transfer element  24 , thereby being cooled. The blood then continues to flow distally into the selected organ, thereby cooling the organ.  
         [0040]    A second embodiment of the heat transfer element is shown in FIG. 2. This embodiment can be constructed of a tubular material such as nitinol, which has a temperature dependent shape memory. The heat transfer element  28  can be originally shaped like the flexible tube  24  shown in FIG. 1, at room temperature, but trained to take on the coiled tubular shape shown in FIG. 2 at a lower temperature. This allows easier insertion of the catheter assembly  10  through the vascular system of the patient, with the essentially straight but flexible tubular shape, similar to the flexible tube  24 . Then, when the heat transfer element is at the desired location in the feeding artery, such as the internal carotid artery, refrigerant flow is commenced. As the expanding refrigerant, such as a 50/50 mixture of pentafluoroethane and 1,1,1 trifluoroethane or a 50/50 mixture of difluoromethane and pentafluoroethane, cools the heat transfer element down, the heat transfer element takes on the shape of the heat transfer coil  28  shown in FIG. 2. This enhances the heat transfer capacity, while limiting the length of the heat transfer element.  
         [0041]    A third embodiment of the expansion element and the heat transfer element is shown in FIG. 3. This embodiment of the expansion element is an orifice  30 , shown at the distal end of the refrigerant supply conduit  20 . The outlet of the orifice  30  discharges into an expansion chamber  32 . In this embodiment, the heat transfer element is a plurality of hollow tubes  34  leading from the expansion chamber  32  to the refrigerant return lumen  19  of the catheter body  18 . This embodiment of the heat transfer element  34  can be constructed of a tubular material such as nitinol, which has a temperature dependent shape memory, or some other tubular material having a permanent bias toward a curved shape. The heat transfer element tubes  34  can be essentially straight, originally, at room temperature, but trained to take on the outwardly flexed “basket” shape shown in FIG. 3 at a lower temperature. This allows easier insertion of the catheter assembly  10  through the vascular system of the patient, with the essentially straight but flexible tubes. Then, when the heat transfer element  34  is at the desired location in the feeding artery, such as the internal carotid artery, refrigerant flow is commenced. As the expanding refrigerant cools the heat transfer element  34  down, the heat transfer element takes on the basket shape shown in FIG. 3. This enhances the heat transfer capacity, while limiting the length of the heat transfer element.  
         [0042]    A fourth embodiment of the heat transfer element is shown in FIG. 4. This embodiment can be constructed of a material such as nitinol. The heat transfer element  36  can be originally shaped as a long loop extending from the distal end of the catheter body  18 , at room temperature, but trained to take on the coiled tubular shape shown in FIG. 4 at a lower temperature, with the heat transfer element  36  coiled around the capillary tube  22 . This allows easier insertion of the catheter assembly  10  through the vascular system of the patient, with the essentially straight but flexible tubular loop shape. Then, when the heat transfer element  36  is at the desired location in the feeding artery, such as the internal carotid artery, refrigerant flow is commenced. As the expanding refrigerant cools the heat transfer element down, the heat transfer element takes on the shape of the coil  36  shown in FIG. 4. This enhances the heat transfer capacity, while limiting the length of the heat transfer element  36 . FIG. 4 further illustrates that a thermocouple  38  can be incorporated into the catheter body  18  for temperature sensing purposes.  
         [0043]    Yet a fifth embodiment of the heat transfer element is shown in FIGS. 5, 6, and  7 . In this embodiment, an expansion element, such as a capillary tube or orifice, is incorporated within the distal end of the catheter body  18 . This embodiment of the heat transfer element can be constructed of a material such as nitinol. The heat transfer element is originally shaped as a long loop  40  extending from the distal end of the catheter body  18 , at room temperature. The long loop  40  has two sides  42 ,  44 , which are substantially straight but flexible at room temperature. The sides  42 ,  44  of the long loop  40  can be trained to take on the double helical shape shown in FIG. 6 at a lower temperature, with the two sides  42 ,  44  of the heat transfer element  40  coiled around each other. Alternatively, the sides  42 ,  44  of the long loop  40  can be trained to take on the looped coil shape shown in FIG. 7 at a lower temperature, with each of the two sides  42 ,  44  of the heat transfer element  40  coiled independently. Either of these shapes allows easy insertion of the catheter assembly  10  through the vascular system of the patient, with the essentially straight but flexible tubular loop shape. Then, when the heat transfer element  40  is at the desired location in the feeding artery, such as the internal carotid artery, refrigerant flow is commenced. As the expanding refrigerant cools the heat transfer element down, the heat transfer element  40  takes on the double helical shape shown in FIG. 6 or the looped coil shape shown in FIG. 7. Both of these configurations enhance the heat transfer capacity, while limiting the length of the heat transfer element  40 .  
         [0044]    As shown in FIGS. 8 through 11, the heat transfer element  24  can have external fins  46 ,  48  attached thereto, such as by welding or brazing, to promote heat transfer. Use of such fins allows the use of a shorter heat transfer element without reducing the heat transfer surface area, or increases the heat transfer surface area for a given length. In FIGS. 8 and 9, a plurality of longitudinal fins  46  are attached to the heat transfer element  24 . The heat transfer element  24  in such an embodiment can have a diameter of approximately 1.0 millimeter, while each of the fins  46  can have a width of approximately 0.5 millimeter and a thickness of approximately 0.12 millimeter. This will give the heat transfer element an overall diameter of approximately 2.0 millimeters, still allowing the catheter to be inserted into the internal carotid artery.  
         [0045]    In FIGS. 10 and 11, a plurality of annular fins  48  are attached to the heat transfer element  24 . The heat transfer element  24  in such an embodiment can have a diameter of approximately 1.0 millimeter, while each of the fins  48  can have a width of approximately 0.5 millimeter and a thickness of approximately 0.12 millimeter. This will give the heat transfer element an overall diameter of approximately 2.0 millimeters, still allowing the catheter to be inserted into the internal carotid artery.  
         [0046]    While the particular invention as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages hereinbefore stated, it is to be understood that this disclosure is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended other than as described in the appended claims.