WO2010105188A2

WO2010105188A2 - Methods and systems for hemostasis using cryotherapy

Info

Publication number: WO2010105188A2
Application number: PCT/US2010/027182
Authority: WO
Inventors: William S. Krimsky
Original assignee: Reset Medical, Inc.
Priority date: 2009-03-12
Filing date: 2010-03-12
Publication date: 2010-09-16
Also published as: WO2010105188A9

Abstract

The present invention provides methods and systems for treating a patient with hemostasis, and initiating or increasing the rate of hemostasis in a tissue in need thereof. The invention also provides systems for delivering or spraying the cryogen to create an isotherm in proximity to the tissue in need of hemostasis. Further, the methods of the invention may comprise utilizing a second method for initiating or increasing the rate of hemostasis such as cauterization or administration of a hemostatic agent.

Description

METHODS AND SYSTEMS FOR HEMOST ASIS USING CRYOTHERAPY

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Application for Patent Serial No. 61/159,476, filed March 12, 2009, the entire contents of which are specifically incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The present invention provides methods and systems for treating a patient in need of hemostasis using cryotherapy, in addition to methods and systems for initiating and/or increasing the rate of hemostasis comprising applying cryogen to the tissue or using cryogen to create an isotherm in proximity to the tissue in need of hemostasis.

BACKGROUND

[0003] Hemostasis refers to the action of reducing and/or stopping the flow of blood and is the result of interaction of various functions: vasocontraction as well as vasoretraction, aggregation of platelets, as well as blood coagulation or clotting. These various functions can be assisted by administering substances which directly or indirectly affect hemostasis, such as vitamin K, astringent agents, thrombin, high-molecular colloids, fibrin foam as well as blood transfusions, substitution of coagulation factors as well as local cooling or the like.

[0004] Blood coagulation is a very complex process which takes place in several stages. The end result is the formation of insoluble fibrin from the fibrinogen which is contained in the blood plasma. This process of fibrin formation is catalyzed by thrombin in interaction with calcium ions. Approximately 30 different factors interact to accomplish blood coagulation, inter alia, the coagulation factors of the blood plasma and numerous platelet factors.

[0005] Hemostasis occurs in two stages: primary hemostasis and secondary hemostasis. In the initial stage, which is generally referred to as primary hemostasis, accumulation and aggregation of platelets occur and the resulting "plug" initially closes the wound to slow down the loss of blood. The accumulation of the platelets and their aggregation are controlled primarily by thromboxane A2. The initial closure of the wound is also assisted by so-called vasoconstricting substances, for example, serotonin, which provide a reduction of the opening of the wound. The aggregation or fusion of the platelets results in the release of the so-called platelet factor 3 which plays an important role in the second stage of hemostasis (secondary hemostasis), the blood coagulation. The process of secondary hemostasis encompasses the sequential activation of plasma coagulation factors leading to the formation of a mechanically stable fibrin thrombus around the initial platelet plug.

[0006] While bleeding is generally an undesirable consequence of any physical trauma, it is usually an inevitable part of surgery, when it may arise as a result of incisions made either at the ultimate site of the surgical procedure or in order to gain physical access to that site. Bleeding may be arterial, venous or capillary, which are conventionally treated in different ways, including electric coagulation (cauterization), or making sutures in the surrounding tissue, around the vessel, or in the vessel wall. Bleeding from large veins can be similarly treated, it is also possible to exert physical pressure at the site of the bleeding in order to staunch the blood flow. Bleeding from small venous vessels and capillaries is most commonly treated during surgery by physically pressing against the bleeding area a compress which may be soaked in saline solution or using a variety of agents that facilitate coagulation. While it is customary to employ sponges or compresses which may be impregnated or soaked with physiological saline solutions to stop bleeding, trying to effect hemostasis in this way is usually time-consuming and requires a large number of sponges or compresses. The use of medical sponges or compresses is moreover limited because hemostasis can be effected only over a limited period of time.

[0007] Another approach to suppress bleeding is the use of antifibrinolytic agents (for example, aminocaproic acid and tranexamic acid), i.e., agents that act to prevent dissolution of fibrin clots. As is known in the medical field, such substances are administered in the form of a solution to be injected or in the form of tablets or pills to be administered orally in the case of hyperfibrinolysis, i.e., increased fibrinolysis as a result of increased levels of plasminogen. They are used to treat serious bleeding, for example, after dental surgery (particularly in patients with hemophilia) or other kinds of surgery and are also given before an operation to prevent serious bleeding in patients. The maximum effect of the application of an antifibrinolytic agent, for example, by means of injection, is reached after about six hours. Side effects such as nausea, vomiting, or diarrhea are observed.

[0008] It is known to use patches or compresses etc. made of cellulose, gelatin, or collagen for effecting hemostasis of bleeding wounds, caused by injury or by surgical intervention. Also known is the application of fibrin adhesives or thrombin. According to all these methods the haemostatic agents are left in situ to be absorbed by the body over a period of one or several weeks.

[0009] Thus, as currently available, hemostasis modalities are all associated with various drawbacks and there remains a need in the art for improved materials and methods. Particularly, in the settings involving trauma, emergency and battlefield situations where an immediate availability of methods to initiate and/or increase the process of hemostasis resulting in a reduction and/or stoppage of bleeding in a very short period of time is critical. This need and others are met by the present invention.

[0010] It was previously shown that cool temperatures did not active coagulating factors (van Oeveren et al, J. Medical Engineering and Technology, 23:20-25). Hence, it is surprising that cryospray treatment, or applying cryogen onto the tissue, as in the instant case, initiated and/or increased the rate of hemostasis.

SUMMARY OF THE INVENTION

[0011] The present invention provides methods and systems for treating a patient in need of hemostasis, comprising applying cryogen to the tissue in a patient in need of hemostasis.

[0012] In one embodiment, the present invention provides methods and systems of initiating or increasing the rate of hemostasis, comprising applying cryogen or using cryogen to create an isotherm in proximity to the tissue in need of hemostasis.

[0013] In some embodiments, the present invention provides methods and systems for reducing and/or stopping bleeding, comprising applying cryogen or using cryogen to create an isotherm in proximity to the tissue in need of hemostasis.

[0014] In some embodiments, the cryogen may be applied directly to the tissue or may be used to create an isotherm in proximity to the tissue in need of hemostasis.

[0015] In some embodiments, the methods of the invention comprise spraying the target tissue with a cryogen or using the cryogen to create an isotherm in proximity to the target tissue to treat a patient in need of hemostasis, and/or to initiate or increase the rate of hemostasis at the target tissue. [0016] In some embodiments, the methods of the invention comprise applying or spraying the target tissue with one or more cryogens, and/or applying or spraying one or more cryogens to create an isotherm in proximity to the target tissue.

[0017] In some embodiments, the hemostasis results from coagulation, for example, via activation of either the intrinsic or extrinsic coagulation cascade.

[0018] In some embodiments, the hemostasis results from ablation of tissue comprising applying cryogen to tissue or using cryogen to create an isotherm in proximity to the tissue.

[0019] In some embodiments, the method comprises contacting the target tissue with the cryogen or maintaining the tissue in proximity to the isotherm for a period of time sufficient to initiate a tissue response.

[0020] Any suitable cryogen may be used. The cryogen may be a liquid having a boiling point temperature lower than the freezing point of the tissue to be treated, or initiate or increase the rate of hemostasis. hi some embodiments, a cryogen may be a liquefied gas, for example, oxygen, a nitrogen oxide, carbon dioxide, nitrogen, argon and room air. The temperature of the isotherm can be adjusted by controlling the rate at which cryogen is delivered. The temperature of the isotherm may be sufficiently depressed from normal body temperature to generate the desired response. Suitable examples of temperatures may include, but are not limited to, from about 4°C to about the boiling point of the cryogen.

[0021] In some embodiments, the cryogen is applied or sprayed using a device comprising a catheter. A proximal end of a catheter is connected to a cryogen source and a distal end of the catheter is placed in proximity to the target tissue and cryogen flows from the source through the distal end of the tube. Optionally, the distal end of the catheter is guided to the tissue using a guiding device. Any suitable guiding device may be used. One example of a guiding device might comprise a video camera and the distal end of the guiding device and/or catheter may be guided to the target tissue by observing the distal end of the catheter and/or guiding device on a video monitor.

[0022] In some embodiments, the cryogen can be applied or sprayed to a target tissue varying in size. For example, the area of the tissue thai the cryogen can be applied or sprayed to can be less than 1 square millimeter. Optionally, the area of the tissue can range from about 1 square millimeter to about 5 square millimeters. Optionally, the area of the tissue can range from about 5 square millimeters to about 10 square millimeters. Optionally, the area of the tissue can range from about 10 square millimeters to about 1 square centimeter. Optionally, the area of the tissue can range from about 1 square centimeter to about 5 square centimeters. Optionally, the area of the tissue can range from about 5 square centimeters to about 10 square centimeters. Optionally, the area of the tissue can be more than about 10 square centimeters.

[0023] In some embodiments, the cryogen is applied or sprayed using a device comprising an endoscope.

[0024] In some embodiments of the invention, the cryotherapy method described herein can be used by itself and/or in conjunction with a surgical procedure.

[0025] In some embodiments, cryotherapy can be performed prior to a surgical procedure.

[0026] In some embodiments, cryotherapy can be performed during a surgical procedure.

[0027] In some embodiments, cryotherapy can be performed after a surgical procedure.

[0028] In some embodiments, the methods of the present invention further comprise utilizing a second method for treating a patient in need of hemostasis.

[0029] In some embodiments, the methods of the present invention further comprise utilizing a second method for initiating or increasing the rate of hemostasis.

[0030] In some embodiments, the methods of the present invention further comprise utilizing a second method for reducing and/or stopping bleeding.

[0031] In some embodiments, the second method may be cauterization, for example electrocautery or chemical cautery.

[0032] In some embodiments, the second method includes administration of an agent known to initiate or increase the rate of hemostasis. Such agents include, but are not limited to, factor VII, factor VIII, factor IX, factor XIII, von Willebrands factor, cryoprecipitate, fresh frozen plasma, platelets, vitamin K, aminocaproic acid, tranexamic acid, desmopressin, aprotinin, adrenalone, adrenochrome, algin, alginic acid, aminochromes, batroxobin, carbazochrome salicylate, cephalins, cotarnine, ellagic acid, ethamsylate, l,2-naphthylamine-4-sulfonic acid, oxamarin, oxidized cellulose, styptic collodion, sulmarin, thrombin, thromboplastin, tolonium chloride, tranexamic acid, vasopressin, vitamin Ic₂, and the like.

[0033] In some embodiments, the agent is administered prior to a surgical procedure.

[0034] In some embodiments, the agent is administered during a surgical procedure.

[0035] In some embodiments, the agent is administered after a surgical procedure.

[0036] The materials and methods of the invention can be useful in, but are not limited to, the emergency, trauma, and military or battlefield setting.

[0037] The cryogen may be applied directly to an affected area of the tissue in need of hemostasis, thereby initiating or increasing the rate of hemostasis, and allowing the bleeding to reduce and/or stop.

BRIEF DESCRIPTION OF THE DRAWINGS

[0038] For the purposes of illustrating the invention, there is shown in the drawings a form which is presently preferred; it being understood, that this invention is not limited to the precise arrangements and instrumentalities shown.

[0039] Fig. IA depicts a bronchoscope inserted into the lung of a patient.

[0040] Fig. IB is an enlarged view of Fig. IA and shows the distal end of the bronchoscope and the catheter within an airway.

[0041] Fig. 2A depicts a close-up of the distal end of a bronchoscope, light source, camera, extra lumen, and lumen with an inserted catheter having an opening for releasing cryogen spray. In the embodiment depicted, the opening of the catheter is at the distal end and the cryogen may exit the catheter in a substantially axial direction.

[0042] Fig. 2B depicts a close-up of the distal end of a bronchoscope, light source, camera, extra lumen, and lumen with an inserted catheter having a lateral opening for emitting directional cryogen spray.

[0043] Fig. 2C depicts a close-up of the distal end of a bronchoscope, light source, camera, extra lumen, and lumen with an inserted catheter having a laterally-disposed, cone-shaped structure for directing cryogen spray. [0044] Fig. 3 is a schematic view of an apparatus for use in respiratory cryosurgery.

[0045] Fig. 4 is a schematic view of an alternative apparatus for use in respiratory cryosurgery.

[0046] Fig. 5 depicts the structure of a heated catheter.

DETAILED DESCRIPTION

[0047] It will be appreciated that the following description is intended to refer to embodiments of a cryosurgical apparatus for use in the methods of the present invention and is not intended to define or limit the invention, other than in the appended claims.

[0048] The invention relates to methods and systems for treating a patient in need of hemostasis. Typically, the methods of the invention will use cryotherapy to initiate and/or modulate the rate of hemostasis. As used herein, cryotherapy includes, but is not limited to, therapies involving decreasing the temperature, for example, hypothermic therapy. The methods also comprise applying cryogen to the tissue in need of hemostasis or using cryogen to create an isotherm in proximity to the tissue. As used herein, hemostasis, includes the stoppage and/or reduction of bleeding or hemorrhage through a blood vessel or organ of the body. The invention also provides methods for slowing or stopping flow of a body fluid or semi-fluid, i.e. fluid stasis or semi-fluid stasis, for example, intestinal stasis, urinary stasis, venous stasis, etc. Application or spraying of cryogen to a tissue can be used to initiate and/or increase the rate of hemostasis, in addition to treating a patient in need of hemostasis.

[0049] The methods described in the present invention can be adapted to situations involving increasing and/or initiating hemostasis, and reducing and/or stopping bleeding in any anatomical area. For example, the methods can be used to initiate hemostasis or increase the rate of hemostasis in the nose, trachea, lungs, mouth, esophagus, stomach, small and large intestines, kidneys, ureters, bladder, urethra, hypothalamus, thyroid, pancreas, ovaries, oviducts, uterus, vagina, mammary glands, testes and penis.

[0050] The methods can be used for treating or increasing the rate of hemostasis and/or initiating hemostasis, and reducing and/or stopping bleeding in any tissue in a mammalian (for example, human) body. Suitable examples of the tissues may be selected from, but are not limited to, epithelial tissue, connective tissue, muscle tissue and nervous tissue. The tissues may include, but are not limited to, tissues of Skeletal System (for example, bones, cartilage, tendons and ligaments), Muscular System (for example, skeletal muscles and smooth muscles), Circulatory System (for example, heart and blood vessels), Nervous System (for example, brain, spinal cord and peripheral nerves), Respiratory System (for example, nose, trachea and lungs), Digestive System (for example, mouth, esophagus, stomach, small and large intestines), Excretory System (for example, kidneys, ureters, bladder and urethra), Endocrine System (for example, hypothalamus, pituitary, thyroid, pancreas and adrenal glands), Reproductive System (for example, ovaries, oviducts, uterus, vagina, mammary glands, testes, seminal vesicles and penis), and Lymphatic System (for example, lymph, lymph nodes and vessels).

[0051] The methods described herein can be useful in various situations including, but not limited to, bleeding during surgery or internal/external bleeding caused by trauma. The surgery may open or closed, for example open heart surgery or surgeries involving endoscopic procedures. Additional applications of the methods include, but are not limited to, internal bleeding caused due to bone fractures, ulcers, certain drugs or internal/external bleeding due to blunt force trauma.

[0052] For example, bleeding can be due to invasive procedures, including, but not limited to surgeries involving nose, trachea, lungs, mouth, esophagus, stomach, small and large intestines, kidneys, ureters, bladder, urethra, hypothalamus, thyroid, pancreas, ovaries, oviducts, uterus, vagina, mammary glands, testes, seminal vesicles, penis, lymph nodes and lymph vessels.

[0053] Further, the current methods can be applied to bleeding associated with inflammation (esophagitis, gastritis, irritable bowel syndrome), enlarged verins (varices), tears (for example, Mallory- Weiss syndrome), ulcers (including in esophagus, stomach, small intestine, duodenal, ulcerative colitis), cancers and infections of various organs, liver disease, hemorrhoids, colorectal polyps, diverticular disease, uremic patients, and gastrointestinal bleeding, hemorrhage associated with hemodialysis patients, gastroduodenal bleeding (for example, in chronic renal failure) and bleeding risks associated with anti-coagulant therapy.

[0054] The methods and systems described in the present invention can be particularly useful in a military or battlefield setting, both for internal bleeding, for example, due to trauma and/or for external bleeding due to any type of wounds (for example, gunshot wounds). [0055] In some embodiments, for example in open surgical procedures, the application of cryogen can generate gas and/or vapor. Such gas and/or vapor can be provided with a mechanism to escape in order to maximize the visibility of the area to be treated. Escape mechanisms can include, but are not limited to, suctioning off the gas with a suction tube or by simple fanning mechanisms. In some embodiments, the gas is not suctioned off or the gas is trapped, to aid in the increase of pressure as considered necessary by the physician.

[0056] In some embodiments of the invention, the cryohemostasis procedure, i.e. initiating or increasing the rate of hemostasis using cryogen, can be used in conjunction with cryospray ablation procedures, for example removal of unwanted tissue. One advantage of such combination of cryohemostasis with cryospray can be to initiate or increase the rate of hemostasis and/or minimize bleeding at the site of cryospray ablation.

[0057] In some embodiments of the invention, the methods and systems described herein can be utilized in any endoscopic surgical procedure. In some embodiments, a catheter comprising a single lumen or multiple lumens which may or may not have a guiding device integrated within the catheter can be used. In some embodiments, as required by the procedures and as to the knowledge of the surgeon, the guiding device may be introduced through a small incision at a site different from the introduction of the catheter, to provide for visual aid of the procedure.

[0058] Methods of the present invention can be performed using any conventional endoscope. Figures IA and IB provide a schematic representation of a method for achieving hemostasis in pulmonary tissue using a conventional therapeutic bronchoscope 10, as is illustrated in the drawings, or a smaller diagnostic bronchoscope to maximize patient comfort. Alternatively, a specially designed bronchoscope can be used. The distal end 12 of such a bronchoscope 10 is shown in FIGs. 2A, 2B, and 2C, showing an imaging camera lens 14, illuminating light 16, biopsy channel (bore or lumen) 18 with the catheter 20 therein, and an additional lumen 22. An additional catheter may be run through the additional lumen 22, for the delivery of therapeutic or diagnostic agents. The image picked up at the lens 14 is transferred via fiber optics to a monitoring camera 25 (FIG. 3) which sends TV signals via a cable 26 to a conventional monitor 28, where the procedure can be directly visualized by a physician. By virtue of this visualization, the surgeon is able to perform the cryotherapy with respect to respiratory tissues. One skilled in the art will appreciate that other styles of endoscope may be used to treat other tissues. The catheter 20 may protrude from the distal end 12 (i.e., the end first inserted into the respiratory tract or respiratory airways) of the endoscope 10 and may extend to the proximal end 30 (closest to the operator, outside the patient) where a physician's hand Hl can guide the catheter 20. As seen in the monitor image 28 of FIG. 4, the distal end 12 of the catheter 20 maybe bent at an angle.

[0059] The catheter 20 can be coupled to a cryogen source, such as a tube extending near the bottom of a Dewar flask 32 filled with liquid nitrogen or other liquefied gas LG. As shown in Fig. 4, the Dewar flask 32 is closed and the interior space is pressurized with a small air pump 34, which may alternatively be mounted in the container lid or elsewhere.

[0060] FIG. 4 shows schematically that the proximal end of the catheter 20 can be coupled to a tube 35, by a connector such as a standard luer lock 37, and the lower end of the tube 35 is immersed in liquid nitrogen LG while the interior is pressurized by a free-running pressure pump 34 through a tube 38. A pressure gauge 40, or alternatively a safety valve with a preset opening pressure (not shown) may be included. The pressure is selected so as to permit adequate spray from the distal end of the catheter 20. The interior of the Dewar flask 32 is vented through a vent tube 42 which can be opened and closed by a valve operated by the physician's hand H2. FIG. 4 shows the thumb obstructing the end of the vent tube 42. When the vent is closed, pressure builds up in the Dewar flask 32 and the liquefied gas is pumped through the tube 35 to catheter 20.

[0061] The vent tube 42 can be left open until the physician has positioned the catheter near the respiratory tissue, as guided by the hand Hl and confirmed by viewing the monitor 28. The vent 42 is then closed and liquefied gas is pushed into the proximal end of the catheter 20 at the luer lock 37.

[0062] The apparatus shown in Figures 3 and 4 can also be used with the methods of the present invention and is more fully described in U.S. Pat. No. 7,025,762 to Johnston et al., which is hereby incorporated by reference. Other apparatus capable of delivering liquid cryogen to a catheter, particularly low temperature, low pressure cryogen, may also be employed.

[0063] The catheter can be adapted to spray cryogen through one or more openings. When a lateral hole is provided in the wall of the catheter, the distal end of the catheter can be closed so that cryogen is directed laterally. The length of the catheter tip and size and shape of the spray holes can be chosen so that the entire area of the targeted tissue is treated at once without the need for manipulating the scope or catheter to treat the targeted area in sequential increments. The catheter tip may be of rigid material such as metal or stiff plastic, preferably the latter. Alternatively, the entire endoscope and/or catheter may be moved to ensure that the entire targeted area is sprayed.

[0064] The catheters of the present invention can be of a thermoset or a thermoplastic material, may be manufactured from a combination of a number of materials including, but not limited to, stainless steel, metal, nickel alloy, nickel-titanium alloy, hollow cylindrical stock, thermoplastics, high performance engineering resins, polymer, fluorinated ethylene propylene (FEP), polyethylene (PE), polypropylene (PP), polyvinylchloride (PVC), polyurethane, polytetrafluoroethylene (PTFE), polyether-ether ketone (PEEK), polyimide, polyamide, polyphenylene sulfide (PPS), polyphenylene oxide (PPO), polysufone, nylon, perfluoro (propyl vinyl ether) (PFA), polyoxymethylene (POM), polybutylene terephthalate (PBT) or polyether block ester. The catheter is manufactured so as to maintain the desired level of flexibility and torqueability according to multiple embodiments of the current invention. In some embodiments, a catheter for use in the invention may be heated. An example of a heated catheter is shown in Figure 5. US patent no. 7,255,693 discloses an exemplary heated catheter and is specifically incorporated herein by reference.

[0065] In some embodiments, the catheter will have one or more openings, whereby cryogen spray exits the catheter and contacts the tissue. In other embodiments, the openings may be configured in such as way as to allow the cryogen to spray in a substantially perpendicular direction. When used in connection with a spray pattern, the term "substantially perpendicular" is not intended to limit direction of the spray to a plane at an angle of 90 degrees to the axis of the catheter, but includes any type of spray which will allow the targeted tissue, such as the respiratory tract or airway that is coaxial to the catheter to be sprayed, near the locus of the tip of the catheter and to exclude a spray which is only substantially axial. Figures 2A, 2B, and 2C show various openings in the catheters that may be used in the practice of the invention.

[0066] The apparatus utilized in the current methods can comprise a pressurized container in which the internal pressure of the container drives the flow of cryogen. Such a container can have an internal pressure from about 5 psi to 450 psi or more. Further, the container can have internal pressures of from about 20 psi to about 200 psi. The container can be a sealed canister connected to the cryospray apparatus in such a way as to permit the flow of liquefied gas from the canister without entirely releasing the pressure and allowing the cryogen to evaporate. The apparatus may include pressure step down valves or other mechanisms that reduce the pressure of the cryogen exiting the canister in order to allow the cryogen to exit the catheter at low pressure.

[0067] As used in the present specification, "gas" in the phrase "liquefied gas" means any fluid which is physiologically acceptable and which has a sufficiently low boiling point to allow the cryotherapy of the present invention. For example, such boiling point may be below about -150⁰C. Examples of such gases include, but are not limited to, nitrogen, as it is readily available, nitrogen oxides, oxygen, liquid air and argon. Liquefied gas may be used as a cryogen.

[0068] The flow of liquefied gas from the cryogen source may be controlled using any structure known in the art, for example, a simple thumb-valve, a mechanical valve or an electromechanical valve. The valve may be controlled by a trigger mechanism, or the like, as could be readily envisioned and constructed by those of ordinary skill in the art. In an embodiment, an electrically operated solenoid valve may be employed to deliver the liquefied gas to the catheter. The solenoid can be specifically adapted to function properly at low temperatures.

[0069] In some methods, liquid cryogen is not sprayed directly upon a target tissue. Instead, the cryogen is delivered through the distal end of the catheter at a rate such that the cryogen undergoes liquid to gas phase transition before coming into contact with the target tissue. In effect, cryogen is delivered to a site of treatment as a cold gas. The cold gas causes a reduction in the ambient temperature of the region around the distal end of the catheter. As used herein, "isotherm" indicates a region of reduced ambient temperature. Thus, delivery of cryogen can be used to reduce the ambient temperature at a site to be treated. The temperature of the isotherm can be maintained at any desired value by increasing (to reduce temperature) or decreasing (to increase temperature) the rate at which cryogen is delivered through the catheter and exits the distal end of the catheter. The catheter and/or an optional guiding device may be equipped with a temperature sensor in order to monitor the temperature of an isotherm. Optionally, the data from the temperature sensor can be displayed on the control panel. In some embodiments, the data from the temperature sensor is used to control a valve (for example, a solenoid valve as discussed above) that controls the rate of flow of cryogen through the catheter. In such embodiments, the desired temperature of the isotherm may be programmed into the controller and the valve controlled by a feedback loop in order to maintain the desired temperature.

[0070] It is to be noted that the apparatus may be able to initiate a response in and/or freeze tissue sufficiently without actual liquefied gas being sprayed from the catheter, and that a spray of liquid may not be needed if the very cold gas (for example, nitrogen gas at less than 0⁰C) can accomplish the task of freezing the targeted tissue. Thus, an isotherm of sufficiently low temperature can be created and maintained in contact or not in contact (e.g., in proximity) with a target tissue for a period of time sufficient to result in initiating a response in the target tissue.

[0071] In embodiments that involve spraying liquid cryogen directly onto tissue, the cooling rate (rate of heat removal) is much higher than with a solid, contact probe because the sprayed liquefied gas can evaporate directly on the target tissue, which absorbs much of the heat of vaporization. The rate of rewarming is also high, since the applied liquid boils away almost instantly. No cold liquid or solid ultimately remains in contact with the tissue, and the depth of freezing can be minimal if desired.

[0072] Since freezing is accomplished by boiling liquefied gas (e.g., nitrogen), large volumes of this gas can be generated. This gas can be provided with a mechanism to escape in order to minimize the chance of pressure-related injury. To avoid such injuries, the resultant gas can be suctioned off. For example, in endoscopic surgeries, an escape path may be provided by an additional lumen in the endoscope. Additional lumens can provided on so-called "therapeutic" bronchoscopes. The use of a multi-lumen "therapeutic" bronchoscope can provide an extra lumen for use as an escape path for gas venting. The application of suction to such a vent lumen can also be provided. "Diagnostic" bronchoscopes typically have only one lumen, which would be occupied by the liquefied gas-delivery catheter when such a bronchoscope is used. In such situations, an escape path may be provided via active or passive systems. For example, an active system can include a suction tube introduced through a small incision at a site different from the introduction of the catheter that can provide for the exit of gas generated. Suction may be provided by a suction pump, or other conventional suction device.

[0073] The cryogen spray can be conducted in such a manner as to allow constant visualization by the physician of the targeted tissue treatment as it occurs. Such visualization can be direct or indirect. One example of a visualization device is a video camera comprising a lens. Condensation on the lens may be avoided by means of the suction pump, which will immediately suck out the moist air which is present prior to the arrival of the liquid spray or cold gas. This condensation effect is augmented by the fact that the catheter itself may not be wrapped in additional insulation.

[0074] As shown in Figure 4, an electronic monitoring and recording system 90 may also be used with the apparatus during cryosurgery and is describe in US Patent 7,025,762. The electronic components of the system may comprise a control box 99, temperature sensor or probe 92 and timer 96. Also connected to the monitoring and recording system may be a foot- pedal 86 for actuating the solenoid and a recording console. An electric power cord can run from solenoid to the control box. The electronic monitoring and recording system may record the times at which cryofrost starts and ends. Temperature in the treatment space may also be recorded for the cryosurgery at pre-selected time increments. This recordation allows for better data acquisition and documentation. The electronic console can be preprogrammed to be patient specific.

[0075] Figure 4 also depicts a gas supply system 70 comprising a tank 72 equipped with valves and gauges. The tank 72 is equipped with a head gas valve 77 for relieving head pressure and a liquid nitrogen valve 78 which is opened to allow liquid nitrogen to flow to the solenoid valve 80 and then to catheter 20. Pressure building tube 74 allows circulation of cryogen outside of the tank to increase pressure in the tank by heating the cryogen. The system may also comprise a bleeder valve 88.

[0076] The components or paraphernalia required to practice the method of the present invention may be packaged and sold or otherwise provided to health-care providers in the form of a kit.

[0077] Embodiments of the invention will be further illustrated by the following non-limiting examples.

EXAMPLES

Example 1

Hemostasis using cryospray in an endoscopic procedure in airway [0078] Subject: A 59-year-old female with a history of a prior resection of the right lower lobe for non small cell lung carcinoma (NSCLC) with tumor recurrence at stump site, and endoluminal obstruction of right middle lobe and right upper lobe. Figures IA and IB provide a schematic of treatment in the lung according to the present invention.

[0079] Method: The patient was brought to the operating room, placed on 100% oxygen, and a bronchoscope was inserted through her endotracheal tube. Oxygen saturation and peak airway pressure were monitored throughout the procedure. Endoluminal debulking was begun in attempt to reestablish luminal patency.

[0080] Results: After completion of the endoluminal debulking of the tumor several attempts were made to provide hemostasis and control bleeding with frequently used methods such as electrocautery and argon plasma coagulation. However, these were relatively ineffective and bleeding continued. At that point, the scope was appropriately positioned in the treatment area, the cryotherapy catheter was deployed through the bronchoscope and cryotherapy was administered. Two cycles of 5-second spray dosimetry with roughly a 60-second interim thaw were administered to the treatment area. After suctioning, to clear the airway of debris, bleeding had been effectively controlled and confirmed with visualization.

[0081] Conclusions: The results of this procedure demonstrate hemostasis using cryotherapy within a short period of treatment.

[0082] The above described examples demonstrate that cryotherapy is effective for providing hemostasis in a range of human lung diseases.

Example 2

Hemostasis using crvospray in an open surgery

[0083] A patient with necrotizing pneumonia and an empyema underwent resection on the right lower lobe and attendant decortication of the parietal pleura. Given the broad area of general oozing and bleeding that often accompanies these procedures, a cryospray catheter was deployed and the wide area of oozing on the parietal surface of the chest wall was treated with spray cryotherapy.

[0084] The spray cryotherapy effectively staunched the oozing and bleeding from these areas. [0085] All publications, patents and patent applications mentioned in this specification are indicative of the level of skill of those skilled in the art to which this invention pertains, and are herein incorporated by reference to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference.

[0086] Modifications may be made without departing from the basic spirit of the present invention. Accordingly, it will be appreciated by those skilled in the art that within the scope of the appended claims, the invention may be practiced other than has been specifically described herein.

Claims

What is claimed is:

1. A method of initiating or increasing the rate of hemostasis, comprising applying cryogen directly to tissue in need of hemostasis or using cryogen to create an isotherm in proximity to said tissue.

2. The method of claim 1, wherein said cryogen is selected from the group consisting of oxygen, nitrogen dioxide, carbon dioxide, nitrogen, argon or room air.

3. The method of claim 1, wherein said cryogen is a liquid cryogen.

4. The method of claim 3, wherein said liquid cryogen is nitrogen.

5. The method of claim 1 , wherein said hemostasis results from coagulation.

6. The method of claim 1 , wherein said liquid cryogen is sprayed on said tissue.

7. The method of claim 1, wherein said tissue is contacted with cryogen or is in proximity to the isotherm for a period of time sufficient to initiate a tissue response.

8. The method of claim 1 , wherein said method is performed during a surgical procedure.

9. The method of claim 6, wherein said liquid cryogen is applied using a device comprising an endoscope.

10. The method of claim 6, wherein said liquid cryogen is applied at low pressure.

11. The method of claim 6, wherein said liquid cryogen is applied using a device comprising a catheter.

12. The method of claim 10, wherein said catheter is made of a low pressure material.

13. The method of claim 11, wherein said low pressure material is selected from the group consisting of polytetrafluoroethylene, Pebax, nylon, or polyimide.

14. The method of claim 1, wherein said hemostasis results from an activation of either the intrinsic or extrinsic coagulation cascade.

15. The method of claim 1 , wherein said hemostasis results from ablation of tissue.

16. A method of initiating or increasing the rate of hemostasis, comprising applying cryogen directly to tissue in need of hemostasis or using cryogen to create an isotherm in proximity to said tissue; and utilizing a second method for initiating or increasing the rate of hemostasis.

17. The method of claim 16, wherein said hemostasis results from coagulation

18. The method of claim 16, wherein said second method is cauterization.

19. The method of claim 18, wherein said second method is electrocautery or chemical cautery.

20. The method of claim 16, wherein said second method is administration of an agent known to initiate or increase the rate of hemostasis.

21. The method of claim 20, wherein said agent is selected from a group consisting of factor VIII, factor VII, von Willebrands factor, cryoprecipitate, fresh frozen plasma, platelets, vitamin K, Aminocaproic acid, tranexamic acid, desmopressin, and aprotinin.

22. The method of claim 16, wherein said agent is administered prior to a surgical procedure.

23. The method of claim 16, wherein said agent is administered during a surgical procedure.

24. The method of claim 16, wherein said second method is performed prior to said application of liquid cryogen.

25. The method of claim 16, wherein said cryogen is selected from the group consisting of oxygen, nitrogen dioxide, carbon dioxide, nitrogen, argon or room air.

26. The method of claim 16, wherein said cryogen is a liquid cryogen.

27. The method of claim 26, wherein said liquid cryogen is nitrogen.

28. The method of claim 16, wherein said hemostasis results from coagulation.

29. The method of claim 16, wherein said liquid cryogen is sprayed on said tissue.

30. The method of claim 16, wherein said tissue is contacted with cryogen or is in proximity to the isotherm for a period of time sufficient to initiate a tissue response.

31. The method of claim 16, wherein said method is performed during a surgical procedure.

32. The method of claim 29, wherein said liquid cryogen is applied using a device comprising an endoscope.

33. The method of claim 29, wherein said liquid cryogen is applied at low pressure.

34. The method of claim 29, wherein said liquid cryogen is applied using a device comprising a catheter.

35. The method of claim 34, wherein said catheter is made of a low pressure material.

36. The method of claim 35, wherein said low pressure material is selected from the group consisting of polytetrafluoroethylene, Pebax, nylon, or polyimide.

37. The method of claim 16, wherein said hemostasis results from an activation of either the intrinsic or extrinsic coagulation cascade.

38. The method of claim 16, wherein said hemostasis results from ablation of tissue.

39. A method of treating a patient in need of hemostasis, comprising applying liquid cryogen directly to tissue in need of hemostasis.

40. The method of claim 39, wherein said cryogen is selected from the group consisting of oxygen, nitrogen dioxide, carbon dioxide, nitrogen, argon or room air.

41. The method of claim 39, wherein said cryogen is a liquid cryogen.

42. The method of claim 41 , wherein said liquid cryogen is nitrogen.

43. The method of claim 39, wherein said hemostasis results from coagulation.

44. The method of claim 39, wherein said liquid cryogen is sprayed on said tissue.

45. The method of claim 39, wherein said tissue is contacted with cryogen or is in proximity to the isotherm for a period of time sufficient to initiate a tissue response.

46. The method of claim 39, wherein said method is performed during a surgical procedure.

47. The method of claim 44, wherein said liquid cryogen is applied using a device comprising an endoscope.

48. The method of claim 44, wherein said liquid cryogen is applied at low pressure.

49. The method of claim 44, wherein said liquid cryogen is applied using a device comprising a catheter.

50. The method of claim 49, wherein said catheter is made of a low pressure material.

51. The method of claim 50, wherein said low pressure material is selected from the group consisting of polytetrafluoroethylene, Pebax, nylon, or polyimide.

52. The method of claim 39, wherein said hemostasis results from an activation of either the intrinsic or extrinsic coagulation cascade.

53. The method of claim 39, wherein said hemostasis results from ablation of tissue.

54. The method of claim 39, wherein said method also includes utilizing a second method for initiating or increasing the rate of hemostasis.

55. The method of claim 54, wherein said hemostasis results from coagulation

56. The method of claim 54, wherein said second method is cauterization.

57. The method of claim 56, wherein said second method is electrocautery or chemical cautery.

58. The method of claim 54, wherein said second method is administration of an agent known to initiate or increase the rate of hemostasis.

59. The method of claim 58, wherein said agent is selected from a group consisting of factor VIII, factor VII, von Willebrands factor, cryoprecipitate, fresh frozen plasma, platelets, vitamin K, Aminocaproic acid, tranexamic acid, desmopressin, thrombin, fibrinogen, factor X and aprotinin.

60. The method of claim 54, wherein said agent is administered prior to a surgical procedure.

61. The method of claim 54, wherein said agent is administered during a surgical procedure.

62. The method of claim 54, wherein said second method is performed prior to application of liquid cryogen.

3. The method of claim 54, wherein said second method is performed after application of liquid cryogen.