Patent Application
20240000067
None.
The present application relates generally to devices for use during surgical procedures, e.g., organ transplant procedures, and, more particularly, to temperature regulating devices to maintain desired preoperative and/or intraoperative temperatures to transplanted organs, such as kidneys, and to methods for using such devices.
Kidney transplantation is the best current treatment for kidney failure. However, one out of three (33%) of kidney transplant patients experience delayed graft function (“DGF”), which is defined as a transplant recipient requiring dialysis within seven days of transplantation surgery. Patients that develop DGF have longer hospitalizations, increased rates of rejection, and shorter graft survival by an estimated three to five (3-5) years. Premature graft failure in these patients means a return to long-term dialysis and increased morbidity, from continued immunosuppression therapy or transplantectomy, without the benefits of transplantation.
The mechanism underlying DGF is thought to be related to ischemic damage sustained in the time period between organ procurement and transplantation. Renal metabolism is predominantly aerobic which makes it especially susceptible to anoxic damage and ischemia. Hypothermia protects against anoxia by significantly reducing the energy dependent metabolic activities of the kidney. Optimal renal hypothermia for transplantation is achieved at about one to two degrees Celsius (1-2° C.), and about four to eight degrees Celsius (4-8° C.) for machine based cold-perfusion. Transplant teams use this preservative effect as soon as an organ is removed from a donor and during transport. Cadaver kidneys are routinely packaged and maintained at less than four degrees Celsius (4° C.). However, during the recipient transplantation surgery, there are no effective methods to prevent re-warming and the anoxic damage that subsequently occurs. Kidney warming above the threshold of necrosis begins as early as ten minutes into a surgical anastomosis procedure. Warming of a donor kidney during the sew-in period of a transplant, i.e., second warm ischemia time (“SWIT”), is independently associated with higher rates of delayed graft function, premature graft failure, and a lower acceptance rate of higher-risk kidneys by surgeons. SWIT is protracted in patients and kidneys with complex anatomy, pediatric patients, in minimally invasive surgery, and in patients with obesity.
Reducing SWIT to less than thirty minutes (30 min) reduces the risk of DGF by 3.5-fold. Furthermore, elimination of warm ischemia by graft cooling during implantation to a target temperature of about four degrees Celsius (4° C.) reduces metabolism in the majority of cells to about five to eight percent (5-8%) of normal levels and diminishes enzyme activity, thereby minimizing ischemic injury. This significantly reduces the of DGF and improves organ function.
There remains a need for a reliable approach to control the temperature of organs during transplantation surgery. Devices or methods capable of regulating the temperature of kidneys or other organs, e.g., before and/or during transplantation procedures, would be useful.
The present application is directed to medical devices related to organ transplant procedures, and, more particularly, to devices for facilitating surgery involving transplanted organs and/or for hypothermic treatment of organs, e.g., to maintain desired preoperative and/or intraoperative temperatures to transplanted organs, such as kidneys, and to methods for using such devices, e.g., to improve workflow during surgical procedures.
The devices and methods herein may facilitate intraoperative handling of a kidney or other organ during surgery. Inadvertent slippage of the organ may be reduced and the devices may be attached to retractors (e.g., Bookwalter or Thompson retractors) and/or attached or clamped to the surgical drapes, which may free both hands of an assistant to more effectively assist a surgeon during vascular anastomosis. Additional device attributes, such as a retraction handle, temperature sensor, and an orientation indicator, may provide visual and tactile support to the surgeon during the anastomosis. In some examples, the devices have no tubing or attachments that could impede a transplantation surgeon as they work. The devices may be less bulky than conventional devices, particularly those that have external tubing that may get in the way, e.g., of the fine sutures that are used during anastomosis. Conventional devices may not cool the organ for long enough and/or consistently, may change the workflow of the procedure, and may not be used easily in obese patients or patients with difficult anatomy.
In accordance with one example, a device is provided for regulating the temperature of an organ being transplanted from a donor to a recipient, e.g., preoperatively or intraoperatively, that includes a housing including one or more walls surrounding an interior cavity sized to receive an organ and an opening for accessing the cavity, wherein one or more of the walls includes an inner layer defining an inner surface for contacting the organ placed in the cavity, an outer, e.g., insulation, layer defining an outer surface of the housing, and a cooling layer between the inner and outer layers configured to absorb thermal energy from the organ within the cavity through the inner layer.
In accordance with another example, a device is provided for regulating temperature of an organ that includes a housing including one or more walls surrounding an interior cavity sized to receive an organ and an opening for accessing the cavity, one or more of the walls including a cooling layer comprising a phase-change material configured to absorb thermal energy from the organ within the cavity through the inner layer.
Optionally, in any of the devices herein, the outer wall may include material having a low thermal conductivity to minimize exposure of the cooling layer to exterior temperatures.
Optionally, in any of the devices herein, the inner wall may include material having a high thermal conductivity to maximize exposure of the organ to the cooling layer.
Optionally, the devices may include one or more fasteners for at least partially closing the opening to secure the organ received within the cavity, e.g., a pair of straps extending from one edge of the opening adjacent one another that may be secured to the housing across the opening.
Optionally, the devices may include a handle extending from the housing to facilitate manipulation of the housing, e.g., that extends from a back wall of the housing generally opposite the opening.
Optionally, the devices may include an indicator on the housing configured to provide a visual indication of an anatomical orientation of the organ received within the cavity.
Optionally, the devices may include a temperature sensor adjacent to the inner surface for measuring temperature of the organ received in the cavity, and an output device to provide an output of the measured temperature.
Optionally, the devices may include a timer configured to be activated during a surgical procedure to provide an indication of elapsed time during the procedure.
Optionally, the devices may include one or more sensors adjacent the inner surface for measuring one or more characteristics of the organ received in the cavity, such as an ultrasound or doppler sensor, a sensor configured to assess one or more of assess vascular flow metrics, resistive indices, kidney appearance, or to acquire sub-capsular images, and/or a temperature sensor for measuring temperature of the organ received in the cavity. Optionally, the device may include a wireless transmitter for transmitting data acquired by the sensor(s) to a remote device.
Optionally, the devices may include a GPS tracking device mounted on the housing to allow the location of the device to be monitored.
Optionally, the devices may include one or more lights adjacent to the opening, e.g., to illuminate a surgical field adjacent the opening.
In accordance with another example, a method is provided for cooling an organ, providing a housing comprising one or more walls surrounding an interior cavity, wherein one or more of the walls comprises an outer insulative layer and a cooling layer adjacent to an inner surface of the cavity; and placing an organ within the cavity.
Other aspects and features of the present invention will become apparent from consideration of the following description taken in conjunction with the accompanying drawings.
The invention is best understood from the following detailed description when read in conjunction with the accompanying drawings. It is emphasized that, according to common practice, the various features and design elements of the drawings are not to-scale. On the contrary, the dimensions of the various features and design elements are arbitrarily expanded or reduced for clarity. Included in the drawings are the following figures.
Before the examples are described, it is to be understood that the invention is not limited to particular examples described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular examples only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.
Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and exemplary methods and materials are now described.
It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound” includes a plurality of such compounds and reference to “the polymer” includes reference to one or more polymers and equivalents thereof known to those skilled in the art, and so forth.
Certain ranges are presented herein with numerical values being preceded by the term “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.
The kidneys of patients with End-Stage Renal Disease (“ESRD”) are not working well enough to sustain life. The current treatment for the patient's life-threatening condition is long-term dialysis or a kidney transplant. A kidney transplant is the optimum treatment for these patients because life expectancy increases significantly for those who receive a transplant when compared to those receiving long-term dialysis.
The current standard of care (“SOC”) for kidney transplantation begins when a surgeon removes a kidney from a donor. When the kidney stops receiving oxygenated blood, the cells initiate anaerobic metabolism leading to the depletion of ATP stores and release of damaging byproducts. These events cause cell death and organ dysfunction and need to be mitigated for many hours to preserve the viability of the donor kidney for the recipient. Cooling is a well-understood method to mitigate ischemic injury and preserve the viability of a donor kidney. Lowering the temperature of the donor kidney to between about two and six degrees Celsius (2-6° C.) as quickly as possible, without causing the cells to freeze and rupture, slows down anaerobic metabolism, which in turn slows down progression to cell death. For the purpose of discussing current SOC for hypothermic treatment of the recipient's kidney after it has been removed from the donor,
One goal of the clinical teams involved in each stage of the transplantation process is to reduce warm ischemic injury, i.e., the time the kidney spends at elevated temperatures without being perfused with blood and oxygen. In Stage 1, transplant teams attempt to slow down ischemic injury by extracting the kidney from the donor and cooling the organ by putting it on ice immediately or via other methods of cooling. The goal is to reduce the temperature of the kidney from body temperature (displayed as thirty-seven degrees Celsius (37° C.) in
In Stage 2, the kidney is transported from the donor to the intended recipient with ESRD. The recipient may be located in the same hospital as the donor or across the country; therefore, the duration of Stage 2 varies typically between about two and eighteen (2-18) hours (or longer). Fortunately, multiple FDA-cleared devices are indicated for safe and effective hypothermic treatment of the kidney during Stage 2. These devices are capable of maintaining the organ at the target temperature during transportation.
Devices are needed for the hypothermic treatment of a donor kidney during Stage 3—Transplantee Surgery. The second warm ischemic injury (“SWII”) that occurs during Stage 3 has been linked to poor short- and long-term outcomes for the recipient and premature failure of the transplanted kidney. The SWII also contributes to the reduction in the available pool of donor kidneys since ischemic injury is cumulative, that is, the SWII adds to the FWII. Transplant surgeons are aware of this fact, thus increasing the number of donor kidneys they reject for their patients (e.g., those obtained from donors who die after cardiac events). In addition to the direct injury to the recipient's kidney caused by the SWII, an indirect injury to the recipient may result from the time-sensitive nature of the transplantation procedure. Surgeons are aware of the SWII and thus work to complete anastomosis as quickly as possible, which in turn can lead to mistakes and surgical complications.
SOC for mitigating the effects of the SWII during Stage 3 is to wrap the kidney in gauze and ice as the recipient is prepared for surgery, e.g., as shown in
Turning to
Although the devices and methods herein are generally described with particular reference to kidney transplantation, it will be appreciated that the devices and methods may be used for transplantation of other organs, e.g., hearts, lungs, or livers, or grafts and/or other structures, such as heart valves, vascular grafts, extremities, or other body parts, and the like. Additionally, the devices herein may be used to surround or store bags or other containers of fluid solution, preservation solutions, blood, plasma, medications, and/or other temperature-sensitive materials that are used in transplant or other surgeries (e.g., during procurement, transport, and/or recipient surgery), or in other fields of patient care in order to maintain the material at a desired temperature for a desired duration. For example, the devices may be used to cover or contain preservation solutions to cool them during a procurement period and/or when flushing a donor organ during back-table preparation.
Generally, as shown in
In addition or alternatively, the walls 22, 24 may be rounded and/or otherwise shaped to receive the kidney with minimal airspace within the cavity 26. For example,
Returning to
With additional reference to
In one example, the inner layer 30 and outer layer 40 may be formed from flexible material, e.g., polymer material such as hydrogel, elastomeric material such as silicone, and the like. The material may be elastic and/or otherwise stretchable or may be inelastic, e.g., having a defined size and shape. The inner layer 30 may have a thickness and/or relatively high thermal conductivity to readily transfer thermal energy from the organ 90 received in the cavity 20 to the cooling layer 50. Conversely, the outer layer 40 may have a thickness and/or relatively low thermal conductivity to minimize exposure of the cooling layer 50 to exterior temperatures. The inner and outer layers 30, 40 may be formed separately and then permanently attached together, e.g., by one or more bonding with adhesive, fusing, sonic welding, and the like, or may be integrally formed together, e.g., by molding, casting, 3D printing, and the like.
In addition or alternatively, other materials may be included in the housing 20, e.g., woven textiles, ceramic fibers, and the like, e.g., to provide desired thermal characteristics and/or to provide desired finishes for the inner and/or outer surfaces 32, 42 of the housing 20. Optionally, the outer layer 40 may include one or more additional insulating features, e.g., air pockets, foam fillers, and the like (not shown) to reduce the thermal conductivity of the outer layer 40. In addition or alternatively, one or more walls may include biasing mechanisms, e.g., one or more band springs or other structures (not shown) embedded within or otherwise attached to the wall(s) to provide a desired shape and/or structural integrity to the housing 20, e.g., if the wall(s) are formed from elastic or stretchable material. Optionally, such biasing mechanisms may be expandable, e.g., such that the housing 20 may be stretched or otherwise expanded to accommodate receiving an organ within the cavity 26. Upon release, the biasing mechanism may compress the housing 20, e.g., to minimize airspace around the organ 90 and/or otherwise enhance securing the organ 90 within the housing 20.
The cooling layer 50 may include phase-change material composed to maintain the cavity 26 and the organ 90 therein within a desired temperature range, e.g., between about one and seven degrees Celsius (1-7° C.), between about two and six degrees Celsius (2-6° C.), or about four degrees Celsius (4° C.). The phase-change material may include a phase-change gel, i.e., that absorbs thermal energy by changing from a solid phase to a liquid phase. During this phase change, the phase-change gel maintains a substantially constant temperature, thereby absorbing thermal energy from the organ 90 through the inner layer 30 to maintain the organ 90 within the desired temperature range. Exemplary materials for the phase-change gel may include known biocompatible phase-change gels, such as 1-Decanol (Decyl alcohol), n-tetradecane (n-TD), and the like.
In the example shown in
In a further alternative, the phase-change material may be received in separate pockets or chambers within the walls of the housing 20, e.g., in sealed packets that may be removable or permanently secured within the housing 20 (not shown). For example, if the device 10 is reusable, the phase-change material from a previous procedure may be removed and replaced with fresh phase-change material, e.g., after cleaning and sterilizing the housing 20. Otherwise, if the device 10 is single-use, the phase-change material may be permanently sealed within the walls of the housing 20 such that the entire device 10 is discarded after a procedure.
The thickness of the cooling layer 50 and location of the phase-change material may be selected to provide a desired volume of phase-change material around the cavity 26 to maintain the desired temperature of the organ 90 for a desired length of time, e.g., between about forty-five and seventy minutes (45-70 min), between about twenty and sixty minutes (20-60 min), between about thirty and sixty minutes (30-60 min), or longer if desired, e.g., for extended transportation time periods. In one example, the cooling layer 50 may have a thickness between about one tenth and three centimeters (0.1-3.0 cm) or between about one and three centimeters (1.0-3.0 cm).
Optionally, the device 10 may include one or more features to facilitate manipulation of the device 10. For example, as shown, a handle 60 may be provided on the housing 20, e.g., removably mounted to the back wall 24, e.g., as best seen in
The base plate 62 and back wall 24 may include one or more cooperating connectors, e.g., detents, clasps, and the like (not shown), to mechanically secure the handle 60 to the housing 20, while allowing the handle 60 to be removed if desired. In addition, if the housing 20 includes one or more sensors or other electrical components (e.g., as described elsewhere herein), the base plate 62 and back wall 24 may include one or more electrical connectors that are coupled together when the handle 60 is attached to the housing 20. Such a removable handle 60 may facilitate manipulation while being removable when not needed, e.g., to facilitate storage and/minimize the profile of the device 10. Alternatively, the handle 60 may be permanently attached to the housing 20, e.g., to the back wall 24 by one or more of bonding with adhesives, fusing, welding, mechanical connectors, and the like (not shown).
Optionally, as best seen in
Optionally, the device 10 may include one or more fasteners or other features for at least partially closing the opening 28 and/or otherwise securing an organ 90 received within the cavity 26. For example, as shown in
The free ends 74 of the straps 70 and the housing 20 may include cooperating connectors for securing the straps 70 to the housing 20 such that the straps 70 may be extended across the opening 28 and secured, thereby preventing the organ 90 from falling out or being removed from the cavity 26. For example, as best seen in
As shown, the straps 70 are attached along the same edge of the opening 28 and are spaced apart from one another such that a portion 29 of the opening 28 remains open between the straps to allow vessels or other structures 92 from the organ 90 received within the cavity to extend from the housing 20. For example, if the organ 90 is a kidney, the iliac vessels 92 may extend from the central portion 29 of the opening 28, which may facilitate completing an anastomosis procedure without having to remove the kidney 90, as described further elsewhere herein.
Although the eyelets 76 and posts 68 are shown, it will be appreciated that the connectors may be reversed or other connectors may be provided on the free ends 74 of the straps 70 and the housing 20, such as clips, snaps, magnets, and the like (not shown). In addition, the connectors on the housing 20 may be provided at other locations on the outer surface 32, rather than on the base plate 62 of the handle 60, and the lengths of the straps 70 may be modified to accommodate other locations. In addition or alternatively, a plurality of connectors, e.g., a row of posts or eyelets (not shown), may be provided on the housing 20 and/or on the straps 70 that allow the straps 70 to be secured to the housing 20 at one or more locations, e.g., to allow the straps 70 to be tighter and/or further close the opening 28 before securing the connectors.
Alternatively, as shown in
Optionally, the device 10 of
In addition or alternatively, the device 10 may include one or more straps, pockets, or other features (not shown) to facilitate storage and/or control exposure of one or more structures extending from the organ 90 received in the cavity 26. For example, in the case of a kidney, it may be desirable to expose the renal vessels 92, e.g., to facilitate anastomosis to the recipient's iliac vessels, while holding the kidney's hilar fat and/or ureter out of the way, e.g., by securing the ureter adjacent or within the opening 28.
Optionally, the device 10 of
Optionally, the device 10 of
Optionally, the device 10 of
Turning to
Optionally, the device 10 may be used during the organ procurement and/or transportation periods, e.g. to maintain the organ 90 within a specific temperature range and/or to provide information on temperature variance during transportation. In addition or alternatively, the device 10 may be used during the back-table preparation of the organ 90 prior to implantation into the recipient.
Before use, the device 10 may be stored in a freezer, refrigerator, and/or under other conditions, e.g., to prevent the phase-change material or other coolant from warming. When the device 10 is to be used, e.g., immediately before or during any stage of the transplantation procedure, the device 10 may be removed from storage and allowed to adopt an appropriate temperature for receiving the organ 90.
For example, during exposure of the iliac vessels in the recipient, the device 10 may be removed from the freezer and placed on ice or within a slush machine for a defined time period. Immediately prior to anastomosis, the organ 90 may be removed from the slush solution, placed within the cavity 26 of the device 10, and the securing straps 70 may be applied to hold the organ 90 inside the device 10, e.g., as shown in
Optionally, a timer on the device 10 may be activated to initiate tracking of the anastomosis time and/or organ surface temperature measurements. With respect to kidney transplants, the device 10 may hold the kidney 90 such that the renal vein and renal artery 92 are exposed, and the device 10 may be positioned adjacent the recipient's body such that the renal vein and renal artery 92 of the kidney 90 are easily accessible for sew-in while the kidney 90 remains inside the device 10 and cool, e.g., as shown in
Following completion of the anastomosis and unclamping of the recipient's iliac artery and vein, the timer on the device 10 (if included) may be pressed again to signal the end of anastomosis, and the total anastomosis time may then be recorded. As shown in
Ureter anastomosis to the bladder and/or other remaining procedures may then proceed per SOC. Optionally, the organ 90 may remain within the device 20 after completing the anastomosis procedure, e.g., while perfusing the organ 90 and/or to regulate rewarming of the organ post-procedure.
Turning to
With this housing 20′, the side edges of the walls 22a′, 22b′ extending from the common end 23′ may remain separate, e.g., simply placed adjacent one another and/or partially overlapped. Alternatively, one or more drawstrings, clasps, and/or other connectors (not shown) may be provided along the side edges that may be connected to close and/or further secure the side edges together. Once the organ 90 is secured within the housing 20,′ the device 10′ may be used similar to other devices herein.
Turning to
Turning to
Unlike the previous devices, the cooling component 150 includes an active cooling system including a pump 152, which may be used to circulate coolant within one or more walls of the housing 120, e.g., in an open-loop configuration. For example, the pump 152 may communicate with an external reservoir or other source of coolant 154 and a plurality of fluid channels 154 within one or more walls of the housing 120 (or otherwise provided adjacent the inner surface), e.g., as shown in
Optionally, the pump 152 or reservoir 154 may include a refrigeration or other treatment system, e.g., a heat exchanger (not shown), for removing thermal energy from the coolant, e.g., after being circulated through the channels 156, to maintain the organ 90 at a desired temperature. Alternatively, the reservoir 154 may include a source container of coolant and a water receptacle (not shown) such that coolant from the initial source may be circulated through the channels 156 and then removed and stored without being treated and returned back into the channels 156.
For example, a processor 184 coupled to the pump 152 may include a temperature regulation algorithm that may control operation of the pump 152 and/or reservoir 154 based on signals from the temperature sensor 182 to maintain the target temperature. This may include modifying a flow rate of the coolant through the channels 156 and/or adjusting the temperature of the coolant delivered by the pump 152.
Alternatively, a device may be provided that eliminates any external reservoirs and/or tubing. For example, as shown in
Turning to
Turning to
In describing representative examples, the specification may have presented the method and/or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims.
While the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents and alternatives falling within the scope of the appended claims.
The present application is a continuation of co-pending International Application No. PCT/US2022/021020, filed Mar. 18, 2022, which claims benefit of U.S. provisional applications Ser. No. 63/200,657, filed Mar. 19, 2021, and 63/265,834, filed Dec. 21, 2021, the entire disclosures of which are expressly incorporated by reference.
| Number | Date | Country | |
|---|---|---|---|
| 63200657 | Mar 2021 | US | |
| 63265834 | Dec 2021 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US22/21020 | Mar 2022 | US |
| Child | 18369381 | US |
