WO2020018567A1 - Automated peritoneal organ support - Google Patents

Abstract

Automated peritoneal organ support devices and methods are disclosed herein. One embodiment of a perfusion system may generally include a fluid source for perfusing a fluid within a body cavity of a subject, a catheter defining a distal opening and at least one lumen which is in fluid communication with the fluid source, a fluid waste reservoir for receiving the fluid from the body lumen, and a pH perfusate source having a pH level of at least 8 and which is in fluid communication with the at least one lumen.

Description

AUTOMATED PERITONEAL ORGAN SUPPORT

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 62/699,104 filed July 17, 2018, and U.S. Provisional Application No. 62/856,656 filed June 3, 2019, both of which are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to providing oxygen, and/or reducing C0₂, in the body.

INCORPORATION BY REFERENCE

[0003] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each such individual publication or patent application were specifically and individually indicated to be so incorporated by reference.

BACKGROUND

[0004] Severe trauma is a leading cause of death on the battlefield and one of the leading causes of death in the young adult civilian population. Fatal injuries without any treatment option (e.g., cervical spinal injury and aortic rupture) result in immediate death at the scene. For survivors of the trauma event itself, life-threatening complications in the early course are bleeding, shock and/or severe respiratory failure following chest trauma or massive blood transfusion. The early goal in trauma care is to combat shock. Bleeding shock can be treated effectively on scene by controlling the source of bleeding and rapidly initiating fluid resuscitation. In cases of severe trauma, early damage control surgery and extensive blood transfusion are immediately necessary.

[0005] Extracorporeal Membrane Oxygenation (ECMO) or Extracorporeal Life Support (ECLS) has been successfully used to treat post-traumatic respiratory failure in patients with blunt chest trauma. Published reports have shown success of ECLS support in post- traumatic ARDS (Acute respiratory distress syndrome) patients and severe trauma patients with resistant cardiopulmonary failure and coexisting bleeding shock. While these cases were in the setting of a fully equipped intensive care unit with no resource constraints, they demonstrate the successful extension of this lifesaving technology to trauma patients. [0006] Existing ECMO devices are heavy, bulky and overly cumbersome for field applications. Not only does ECMO require heavy machinery and equipment, it also requires risky cannulation of the large vessels of the body for extracorporeal circulation. Accordingly, developing a small, lightweight, easy to use device for ECMO is critical for effectively treating trauma patients with respiratory failure before they can receive full treatment in the hospital setting

SUMMARY

[0007] The Automated Peritoneal Support (APS) system is a lightweight, compact and easy- to-use treatment for respiratory failure on the battlefield, or elsewhere, such as accidents, etc.

[0008] Post-traumatic respiratory failure, also called acute lung injury, is a common injury on the battlefield and results in a deficit in gas exchange across the alveoli. This deficit leads to acute hypoxia and hypercarbia which, if left unchecked, will lead to death. In the advanced ICU post-traumatic respiratory failure has been successfully treated by ECMO. ECMO, though, requires bulky, heavy equipment and is difficult and risky to initiate even in the most controlled of settings. Peritoneal lavage, using the APS, alternatively, is easy to setup and has been shown to combat hypoxia in four animal studies using three different animal models: dogs, pigs and rats. The APS system achieves superior oxygenation through the use of a pressurized oxygenation chamber/source that supersaturates the circulating lavage/perfusate with oxygen. In addition, or alternatively, C0₂ may be effectively removed from the perfusate solution and/or the patient to reduce C0₂ accumulation in the patient (i.e. reduce the C0₂ of the patient, maintain the C0₂ level of the patient, or minimize the C0₂ level increase of the patient). Other methods of C0₂ reduction are also disclosed herein. Taken together, this combination replaces normal lung function by delivering 0₂ and eliminating C0₂ from the patient via the peritoneal cavity. Alternatively, these functions may be performed separately.

[0009] The APS device may comprise several components: 1) The lavage circuit, including pump and vacuum chamber/source, 2) A source of pressurized oxygen, 3) A sterile access device, 4) sterile, lavage fluid, 5) disposable tubing, and 6) one or more lavage catheters and 7) a controller. Other components may also be included.

[0010] In order to initiate treatment using the APS system, the medic first obtains peritoneal cavity access. This can be done in a relatively bloodless manner with minimal training using a blunt-tipped threaded trocar, which is a simple, safe, timely, and effective approach for gaining peritoneal access. This approach is effective across a wide variety of patients, including the obese and those who had had previous surgery. Furthermore, using a blunt-tipped threaded trocar does not require visual recognition of anatomic layers and may be taught to nonsurgeon physicians, or even non-physicians, who perform peritoneal access.

[0011] The APS device may be used to treat either or both of hypoxemia and hypercapnia.

[0012] One embodiment of a perfusion system may generally comprise a fluid source for perfusing a fluid within a body cavity of a subject, wherein the fluid source has a pH level of at least 8, a catheter defining a distal opening and at least one lumen which is in fluid communication with the fluid source, and a fluid waste reservoir for receiving the fluid from the body cavity.

[0013] One embodiment of a method of perfusing the body cavity of a subject may generally comprise perfusing a fluid from a fluid source and into the body cavity through a catheter which defines a distal opening and at least one lumen which is in fluid communication with the fluid source, wherein the fluid has a pH level of at least 8, reducing an accumulation of C0₂ within the subject via the perfused fluid, and receiving the fluid from the body cavity and into a fluid waste reservoir.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Fig. 1 is an example of a component of a portable Automated Peritoneal Oxygenator device.

[0015] Fig. 2 is an example of a sterile access device.

[0016] Fig. 3 shows the device of Fig. 2 in use to access a body cavity.

[0017] Fig. 4 shows an embodiment of the APS system.

[0018] Fig. 5 shows an embodiment of the APS system which includes continuous, or semi- continuous, C0₂ degassing module and 0₂ aerator module.

[0019] Fig. 6 shows an embodiment of the APS system which is designed to reduce the C0₂ accumulation in the patient.

[0020] Fig. 7 shows an embodiment of the APS system which reconditions and recirculates at least a portion of the perfusate.

[0021] Fig. 8 shows an embodiment of the APS system using vacuum and/or a gas chamber/membrane, connected to a C0₂ degassing module. [0022] Fig. 9 shows an embodiment of the APS system using a C0₂ scrubber.

[0023] Fig. 10 is an example of a data processing system.

DETAILED DESCRIPTION

[0024] An embodiment of the portable, compact APS system is shown in Fig. 1. This system allows for treatment of post-traumatic respiratory failure by exchanging gases utilizing a continuous (or intermittent) fluid oxygen-rich lavage of the peritoneal cavity. The device is light-weight, portable, and easy to use, allowing for field use where conventional ECMO systems are impractical. The device may be under 30 pounds. Alternatively, the device may be under 25 pounds. Alternatively, the device may be under 20 pounds. Alternatively, the device may be under 15 pounds. Alternatively, the device may be under 10 pounds. Alternatively, the device may be under 5 pounds. Alternatively, the device may be under 3 pounds. Alternatively, the device may be under 2 pounds. Alternatively, the device may be under 1 pound.

[0025] Fig. 1 shows the APS component including outgoing oxygenated lavage fluid port 102, which is in fluid communication with oxygen saturation chamber 104. Incoming fluid port 106 is in fluid communication with C0₂ degassing chamber 108. Valve 110 connects the oxygen saturation chamber and the C0₂ degassing chamber. Valve may be a one-way valve and may be passive or controlled by the controller. Display 112 is also shown.

[0026] The APS may be used with 2.5L of isotonic perfusate fluid (i.e. saline) where a 2L volume is indwelling in the peritoneal cavity and 500mL is maintained in the device (being degassed (C0₂ reduced) then oxygenated) at any one time. The volume of 2L was chosen based on the peritoneal dialysis literature showing that the average person can easily receive 2L of fluid in their abdominal cavity without sequelae, however different volumes may be used. The 500mL volume being processed by the device is then infused into the peritoneal cavity via a catheter, while the indwelling fluid is extracted from the peritoneal cavity via either the same catheter (which may be multi-lumen), or a second catheter. If two catheters are used, they may be placed distant from each other within the peritoneal cavity, to ensure that the oxygenated lavage fluid is not extracted before its oxygen is reduced. This extracted fluid is then degassed and oxygenated and the cycle repeats or continues. Alternatively, the device may maintain a different volume of fluid, including around 2L, or around 1L-2L, or around 0.5L-1L of fluid. The fluid may be infused via the more proximal part of the catheter which is within the peritoneal cavity, and extracted via the more distal part of the catheter, or the inverse may be configured.

[0027] In animal studies, it was demonstrated that effective peritoneal gas exchange required an increase of the partial pressure of oxygen (p0₂) in the lavage fluid to about 500mmHg and a reduction in the partial pressure of carbon dioxide (pC0₂) to about lOmmHg.

[0028] Saline may be used as the lavage fluid, or other fluids may be used (or added to saline). For example, fluids with low osmotic activity may be used, such as dextran, polyethylene glycol, albumin, etc. Icodextrin, for example 7.5%, may be added to saline. Fluids which resist absorption within the peritoneal cavity may also be used to increase oxygen transfer.

[0029] In some embodiments a microbubble oxygen formulation may be used as the lavage. In some embodiments, the lavage solution may be supersaturated to a partial pressure of oxygen of around 900mmHg or higher.

[0030] In some embodiments, the APS includes a lavage circuit/controller with the ability to tightly control the incoming and outgoing solution p0₂ and pC0₂. Oxygen and carbon dioxide sensors may be included in line with the in-flow and outflow of the lavage circuit/controller. The lavage fluid entering the device may have a p0₂ of about lOOmmHg and pC0₂ of about 50mmHg. The fluid may be degassed until a pC0₂ of about lOmmHg is achieved. Variables that may be altered to optimize this step may be depth of vacuum, duration of vacuum, geometry of the chamber etc. The lavage fluid may then be transferred to the oxygenation chamber where 0₂ may be bubbled through the fluid until a p0₂ of about 500mmHg is achieved. This step may be optimized based on peak oxygen pressure and duration of exposure.

[0031] Abdominal access may be obtained using the blunt-tipped access device after which a lavage catheter is inserted into the peritoneal cavity. The catheter may be dual-lumen (one lumen for perfusate inflow and one for perfusate outflow), may have a weighted tip, and/or may include pressure sensing capability. More than one catheter may also be used, for example, a separate catheter each for inflow of perfusate and outflow of perfusate.

[0032] An embodiment of blunt- tipped access device 200 is shown in FIGS. 2 and 3. Embodiments of the access device may also include those disclosed in US Application Serial number 16/027,064 filed on July 3^rd, 2018 and US Application Serial number 15/993,483 filed May 30^th 2018, each of which is hereby incorporated by reference in its entirety. For example, the blunt-tipped access device may have threads along a portion of its length to allow advancement of the access device via rotation of the access device. The access device may include one, two or more sensors or electrodes to sense conductance or other properties of tissue as its tip passes through the tissue. These sensors can help identify the type of tissue through which the access device is passing to more safely access the peritoneal cavity without damaging other tissue. The access device may also include a camera.

[0033] Fig. 4 shows an embodiment of the APS in use. Controller 402 controls the system, including the operation of vacuum source/vacuum chamber 404, C0₂ degassing module 406, 0₂ source 408 and the 0₂ aerator module 410, the flow of fluid through the system, (which may include the operation of one or more pumps 412, and/or one or more valves 414), any sensors within the system including 0₂, C0₂ sensors 416 and 418 of the lavage fluid, and 0₂ and/or C0₂ sensor 420 sensing the oxygen and carbon dioxide levels of the patient, etc. The controller also controls the operation of display 422, interfaces 424, etc.

[0034] This embodiment is shown as a closed loop system. In other words, the lavage fluid is cycled from the patient’s peritoneal cavity, into the C0₂ degassing module, into the 0₂ aerator module, and back into the peritoneal cavity. Sensors may be placed throughout the system to control the 0₂ and C0₂ content of the lavage fluid at various stages. For example, C0₂ and/or 0₂ sensors may sense the 0₂ and/or C0₂ content of the lavage fluid as it exits the patient. This measurement will provide the controller information on how much C0₂ needs to be removed from the fluid, and how much 0₂ needs to be added to the fluid. Open looped systems are also envisioned for all embodiments disclosed herein. See Fig. 6 for an example of an open loop system.

[0035] If the sensors sense that C0₂ is higher than desired, then the lavage fluid will be degassed of C0₂ in the C0₂ degassing module. The amount of time in the chamber, or the speed with which the fluid travels through the chamber, or the amount of C0₂ removed is determine by the controller based on the sensed C0₂ levels and any desired level of C0₂. The desired level of C0₂ may be preset by the user, preset by the system, or may depend on other factors. The amount of C0₂ removed may alternatively or additionally be determined by a C0₂ sensor which senses the C0₂ level within the patient’s blood, shown here as a transcutaneous finger sensor, such as a pulse oximeter, and/or other sensor. Blood gas concentrations may be detected via transcutaneous sensors, percutaneous sensors, implanted sensors, etc. Alternatively, or additionally, sensors may sense the gas, such as 0₂ and C0₂, contained in respiration, sweat, urine etc.

[0036] The amount of time that the lavage fluid spends in the C0₂ degassing module may be controlled by one or more valves, by a pump, or by some combination. A C0₂ sensor may sense the C0₂ level of the fluid within the degassing module to determine when the fluid is degassed adequately.

[0037] The C0₂ degassing module may be fluidly connected to a vacuum chamber and/or vacuum source. For example, a vacuum source may be a pump creating a vacuum within a vacuum chamber or directly within the CO₂ degassing module. The pump may be part of the portable system, or may be separate, and/or may be used to prime the vacuum chamber only occasionally. A valve may be incorporated between the vacuum source/chamber and the CO₂ degassing module to control the amount of CO₂ degassing.

[0038] Once the fluid is degassed, it flows to the O₂ aerator module to be saturated or supersaturated with O₂. The amount of added O₂ necessary may be determined by an O₂ sensor of the fluid coming directly from the peritoneal cavity, and/or an O₂ sensor between the CO₂ degassing module and the O₂ module, and/or an O₂ sensor measuring the O₂ level of the patient.

[0039] An O₂ sensor may also be present within the O₂ aerator module itself, to monitor progress of oxygenating the fluid. The amount of O₂ added to the fluid may be controlled by valves, time in the module, amount of O₂ allowed to enter the chamber, the format of the O₂, the configuration of the chamber, the concentration of the O₂ gas, the flow-through rate, etc. CO₂ and/or O₂ sensors may also exist between the CO₂ degassing module and the O₂ aerator module.

[0040] After the lavage fluid has been adequately CO₂ degassed and oxygenated, it flows back into the peritoneal cavity via a catheter, such as catheter 426, or other device. Sensors, such as O₂ and CO₂ sensors may measure the oxygenated perfusate also.

[0041] Valves, controlled by the controller, or passive valves, may be present throughout the system, including those shown in Figs. 4 and 5 and also elsewhere. One pump is shown here on the output side of the O₂ aerator module, but zero, one or more pumps may be present in the system, including on the input side, between modules, etc. Fig. 4 shows the CO₂ degassing occurring before the oxygenation, however, one of these modules may be absent, or the CO₂ degassing may occur after the oxygenation of the fluid, or the two (oxygenation and degassing) may occur simultaneously or semi-simultaneously. The process may also be alternating or continuous.

[0042] One or more pumps may be used to move the fluid through the various stages. The moving of the fluid may be continuous or staged or paused. For example, fluid may be paused while in the degassing chamber and/or oxygen saturation chamber, to allow for equilibrium. One or both chambers may alternatively be elongated so that the fluid moves through continuously and may therefore not be paused, or paused less. The controller may pause or speed the transport of fluid through the various sections/chambers based on readings from the 0₂ and/or C0₂ sensors.

[0043] The adding of fluid and removing of fluid from the peritoneal cavity may be continuous, or may be intermittent. For example, 2L of oxygenated fluid may be perfused into the peritoneal cavity. The fluid may be left there for a set period of time, then the process may be repeated (removing 2L and adding 2L of fluid), or the process may be continuous. The cavity may be kept full, with fluid cycling in and out in approximately equal volumes, or the peritoneal cavity may be intermittently filled and emptied, like a lung. A combination of both methods may also be utilized.

[0044] The controller may also include a display, either integrated into the APS device or remote (wired or wireless). The display may display the status of the fluid gas levels, the status of the patient blood or respiratory gas levels, other patient vital signs, system capacity remaining, including battery charge remaining, 0₂ and vacuum capacity remaining, interface status, etc. The controller of the APS may interface, either via wires or wirelessly, with other systems including mobile phones, tablets, computers, laptops, electronic health/medical records, etc. The controller may also incorporate an alert system including audio, visual, remote, tactile alerts, for any status, including system or patient statuses.

[0045] Trends of the various parameters over time may be displayed, including risk and progression levels. For example, the display may display and alert for developing and/or progressing hypoxemia and/or hypercapnia.

[0046] Fig. 5 shows an embodiment of the APS system which includes continuous, or semi- continuous, C0₂ degassing module and 0₂ aerator module. In this embodiment, lavage fluid flows through the modules in a controlled manner, so that the exposure of the fluid to the vacuum and/or gas is better controlled. The surface area of a flow tube within the chamber is increased via a coil or other configuration, similar to that of a radiator. All or a portion of the walls of the coiled tube may be made from a membrane which is permeable to gas, such as 0₂ and C0₂, but impermeable to liquid, such as saline or water. The walls of the coiled flow tube may be made from a semi-permeable material, which allows gasses to permeate the tubing, but not water. Some examples include PTFE membranes, silicone membranes etc. This allows the control of adding 0₂ into, and removing C0₂ from, the lavage to be controlled by controlling the flow of the fluid through the modules. The rate of fluid flow can be controlled by one or more pumps, and one or more valves. For example, depending on the C0₂ degassing needs of the fluid from the peritoneal cavity, the controller may pass all, or only a portion of the fluid through the C0₂ degassing module. The flow rate of the fluid passing through the module may additionally or alternatively be controlled by a pump. Valves and bypass tube(s) 502 can control the volume or portion of fluid that passes through the module and the volume or portion of fluid that bypasses the module. The same can be done on the 0₂ aerator module.

[0047] Lavage fluid within the system may be ventilated anywhere within the system, for example via a filter, for example, a PTFE or silicone filter.

[0048] The APS system may be powered by an electrical outlet, by a battery, or both. If a battery is present, it may be recharged via solar power.

[0049] Generally, the controller will seek to stabilize the patient as quickly as possible, given the constraints of the system. For example, if battery power, vacuum supply, or 0₂ supply is low, the patient may not be stabilized as quickly as he/she would if the system were adequately supplied. The controller may automatically take into consideration the system constraints, as well as timing requirements (how long the patient needs to be stabilized, or how many patients need to be stabilized), to optimize the stabilization process.

[0050] Several physiological targets may be input into the controller (either manually, or preset, or set by algorithm). These include blood C0₂, 0₂ levels, blood gas ratios, respiratory 0₂, C0₂ levels, respiratory gas ratios, respiratory rate, heart rate, temperature, hematocrit, other blood and respiratory gas levels, oxygenation rate, C0₂ degassing rate, lavage oxygenation level, lavage C0₂ level, peritoneal pressure, etc.

[0051] Arterial blood gases and hematocrit may be measured by the system during the procedure.

[0052] Some embodiments include the ability to perform dialysis on the patient in addition to reducing the patient’s C0₂ and/or increasing the patient’s 0₂ via the APS system to help prevent acute kidney injury or other issues.

[0053] In some embodiments, the APS system reduces the C0₂ levels of the patient without substantially increasing the 0₂ levels of the patient. In some embodiments the APS system both reduces C0₂ and increases 0₂. In some embodiments, the APS system increases 0₂ without substantially decreasing C0₂.

[0054] Reduction of C0₂ [0055] It has been demonstrated that patients with reduced lung function may benefit from C0₂ reduction alone, without substantial 0₂ increase. For example, see“Low-frequency positive- pressure ventilation with extracorporeal C0₂ removal in severe acute respiratory failure” (Gattinoni L, Pesenti A, Mascheroni D, Marcolin R, Fumagalli R, Rossi F, Iapichino G, Romagnoli G, Uziel L, Agostoni A, et al.) which is incorporated herein by reference in its entirety.

[0056] In embodiments which reduce C0₂, the C0₂ reduction may be achieved in any one or more of the following ways:

• Increasing the pH of the perfusate fluid.

• Exposure of the perfusate fluid to a gas such as 0₂ or air.

• Exposing the perfusate fluid to a vacuum.

• C0₂“scrubbing” of the perfusate fluid.

• Other methods may also be used.

[0057] Increasing the pH of the perfusate fluid.

[0058] Carbon dioxide (C0₂) is a by-product of cellular respiration and is dissolved in the blood where it is converted to carbonic acid by carbonic anhydrase. The carbonic acid then dissociates into bicarbonate and hydrogen ions. This process is represented by the following formula:

[0059] Using a higher pH perfusate solution in the peritoneal cavity reduces the C0₂ available to the body and therefor effectively removes C0₂ from the patient via the peritoneal cavity. For example, a dialysate fluid with reduced, or zero, concentration of bicarbonate may be used as the perfusate solution. An example of a zero bicarbonte dialysate solution is included in “Extracorporeal C0₂ removal by hemodialysis: in vitro model and feasibility” (May AG, Sen A, Cove ME, Kellum JA, Federspiel WJ) and is reproduced below:

[0060] It is understood that this is only an example of a high pH perfusate solution. Other formulations may be used. The pH of the perfusate solution using this technique may range from about 8 to about 9. Alternatively, the pH of the perfusate solution using this technique may range from about 9 to about 10. Alternatively, the pH of the perfusate solution using this technique may range from about 10 to about 11. Alternatively, the pH of the perfusate solution using this technique may range from about 11 to about 12. Alternatively, the pH of the perfusate solution using this technique may range from about 12 to about 13. Alternatively, the pH of the perfusate solution using this technique may range from about 13 to about 14. Alternatively, the pH of the perfusate solution using this technique may range from about 8 to about 10. Alternatively, the pH of the perfusate solution using this technique may range from about 9 to about 11. Alternatively, the pH of the perfusate solution using this technique may range from about 10 to about 12.

[0061] Because the perfusion/lavage is occurring within the peritoneal cavity, and not in the blood stream, higher pH solutions may be used than those used for blood dialysis.

[0062] In embodiments where C0₂ reduction is the primary goal (as opposed to 0₂ increase), lower perfusate flow and smaller catheter(s) may be used. The peritoneal perfusion may be continuous or intermittent. For example, a volume of fluid may be introduced into the cavity, allowed to equilibrate with the tissues, effectively removing C0₂ from the subject (or increasing 0₂, in embodiments that include this feature), and then removed after a period of time, or after sensors within the system or monitoring the patient indicate that the fluid should be removed. A sensor or sensors on the access catheter may also be used to monitor the various concentrations of the perfusate over time to determine when the perfusate needs to be replaced or cycled more quickly or slowly. Sensor on the catheter may also monitor pressure, or other parameters.

[0063] Alternatively, the perfusate may flow into and out of the peritoneal cavity of the patient continually at a set rate. The rate of the inflow may or may not be essentially the same as the rate of outflow. Where the fluid is perfused continuously, the perfusion may be for a set period of time at some frequency, for example, for one hour 3 times/week), or the perfusion may be ongoing, for example, with a portable, battery operated device, or in the case of injury. The same pump may be used for both fluid inflow and outflow or separate pumps may be used, or a pump in only one direction may be used (input only or output only).

[0064] The perfusate may be recycled within the system or fresh perfusate may be used and waste perfusate discarded, as in an open loop system. Perfusate recycling may be done by increasing the pH of the perfusate after removal of the perfusate from the peritoneal space and before reintroducing the perfusate fluid back into the patient. The pH of the perfusate may be increased via the addition of a base, such as NaOH, or other methods.

[0065] Fig. 6 shows an embodiment of the APS system which is designed to reduce the C0₂ accumulation in the patient via an open loop system. In an open loop system the perfusate source and waste perfusate are separate. In other words, the perfusate is not recycled or recirculated. It should be noted that because the APS system uses perfusate which is not native to the body (i.e., not blood), the perfusate may be discarded rather than recycled. This is one of the advantages of using the peritoneal cavity to support the lung, or other, function of the patient, instead of using circulating blood, as is used with ECMO systems. An open loop system, or a closed loop system, may be used with any of the embodiments disclosed herein.

[0066] This embodiment may not appreciably increase the 0₂ level of the patient. Shown are high pH perfusate source 602, perfusate waste reservoir 604, pump or pumps 606 which pump perfusate into and/or out of peritoneal cavity 608 via catheter or catheters 610. Source 602 and reservoir 604 may or may not be incorporated into controller 612, or connected to the controller. Display 614 may be incorporated into, or connected to, controller 612. Interfaces connector 616 may be incorporated into, or connected to, controller 612.

[0067] Sensors 618 may sense the chemical and/or pH makeup of the perfusate before entering and after exiting the body. These sensors may be incorporated into the controller or may be separate. In addition, patient sensor 620 may be used to sense the 0₂, C0₂, or other parameter of the patient. The feedback from any of the sensors may be used to control the volume, rate, pressure, flow of the patient perfusion inflow and/or outflow. For example, a high patient C0₂ concentration may trigger the controller to automatically increase the flow rate of the perfusate into the patient and/or out of the patient. Alternatively, the controller may increase the dwell time of the perfusate within the patient. Alternatively, the controller may increase the pH concentration of the perfusate going into the patient. This may be done using optional perfusate mixer 622 which mixes very high pH perfusate with a more neutral perfusate 624 in a controlled manner. The perfusate reservoirs may be incorporated into the controller or be separate from, and connected to, the controller. Alternatively, the controller may increase the volume of perfusate in the peritoneal cavity.

[0068] Fig. 7 shows an embodiment of the APS system which reconditions and recirculates at least a portion of the perfusate. The perfusate is reconditioned by alkalizing module 702 which increases the pH of the perfusate fluid before circulating the fluid back into the peritoneal cavity of the patient. The perfusate may be reconditioned by adding of a base, or by other methods.

[0069] The controller may also control the temperature of the perfusate, so that it is body temperature, higher than body temperature or lower than body temperature. This may be done via a heating element or other ways (not shown).

[0070] The flow rate of perfusate entering the patient may be around 200 mL/min to around 2000 mL/min. Alternatively, the flow rate of the perfusate may be around 200 mL/min to around 400 mL/min. Alternatively, the flow rate of the perfusate may be around 200 mL/min to around 600 mL/min. Alternatively, the flow rate of the perfusate may be around 200 mL/min to around 1000 mL/min.

[0071] The volume of perfusate fluid residing in the peritoneal space of the patient during the procedure may be around 1.5 - 2.5 Liters.

[0072] The duration of the procedure may be minutes, hours or days and may last until lung function is returned.

[0073] The access catheter(s) used in the procedure may be around 3-6 mm in diameter. Alternatively, the access catheter(s) used in the procedure may be around 3-4 mm in diameter. Alternatively, the access catheter(s) used in the procedure may be around 4-6 mm in diameter.

[0074] The pump controlling the inflow of perfusate to the patent may begin before the pump controlling the outflow of used perfusate from the patient to allow for a volume of perfusate to reside in the peritoneal cavity during the procedure. At the end of the procedure, the pump controlling the outflow of perfusate may operate after the pump controlling the inflow of perfusate is no longer pumping so that the peritoneal cavity may be completely empties of perfusate fluid.

[0075] Some embodiments of the APS system may be portable. Some embodiments may be designed to be worn and used by the patient for long periods of time, or even most or all of the time. Some embodiments may operate via a rechargeable battery. Some embodiments may strap onto the patient via a belt, sling, or garment (such as shorts or underwear). Some embodiments may be small enough to clip onto a belt or pants.

[0076] Exposure of the perfusate fluid to a gas such as 0₂ or air.

[0077] In some embodiments the C0₂ concentration within the perfusate is reduced by exposing the perfusate to another gas such as 0₂ or air. This can be done via an oxygenator type membrane (such as those used in extracorporeal membrane oxygenation) or bubbling or other methods.

[0078] Exposing the perfusate fluid to a vacuum.

[0079] In some embodiments of the APS system, C0₂ is reduced in the liquid perfusate by applying a vacuum to the liquid.

[0080] Fig. 8 shows an embodiment of the APS system using vacuum and/or a gas chamber/membrane, connected to C0₂ degassing module 802. The vacuum and/or gas source and/or membrane 804 may be incorporated into the controller, or outside of the controller and connected to the controller.

[0081] C0₂“scrubbing” of the perfusate fluid.

[0082] In some embodiments of the APS system, C0₂ is reduced in the perfusate liquid by “scrubbing” the perfusate. C0₂ scrubbing may be done using a catalyst, amine scrubbing, quicklime, serpentinite, magnesium silicate hydroxide, olivine, molecular sieves, activated carbon, algae, carbonic anhydrase inhibitor, 0_2, or other methods.

[0083] Fig. 9 shows an embodiment of the APS system using C0₂ scrubber 902 to reduce the C0₂ concentration of the perfusate before recirculating the perfusate back into the patient.

[0084] In some embodiments, the controller monitors and controls the pressure within the peritoneal cavity and maintains the pressure at a set pressure. This pressure may be high enough to effectively prevent internal bleeding, for example, by creating a pressure which is higher than the venous pressure or even the arterial pressure. Peritoneal pressure may be maintained at around 1-8 mmHg. In some embodiments, the peritoneal pressure is prevented from going above 8 mmHg.

[0085] Any combination of technologies disclosed herein may be used. For example, a high pH perfusate may be used to reduce the patient’s C0₂ level in combination with increasing the 0₂ level of the patient. Other combinations are also envisioned.

[0086] Some embodiments of the APS system may include support for organs other than the lungs. For example, support for the liver and/or kidneys may be incorporated into the system. Kidney dialysis via the peritoneal cavity may be included. Toxin removal or nutrient supplementation of any kind is envisioned via the perfusing of the peritoneal cavity.

[0087] In some embodiments of the APS system, the catheter or catheters that supply and remove perfusate from the peritoneal cavity may incorporate a mechanism that prevents the opening(s) of the catheter(s) from butting up against tissue, preventing proper function. For example, a catheter which is used for removing perfusate (which may be the same catheter which supplies the perfusate, or may be a separate catheter or a separate opening of the same catheter) may incorporate a mechanism to prevent its being obstructed by tissue. Examples of mechanisms may include a wire, polymer, or other material cage which allows fluid flow through its openings, but holds the openings of the catheter away from body tissue. Another example of a mechanism may be a catheter with multiple arms and/or multiple openings so that if some of the openings are obstructed, other openings will not be obstructed.

[0088] Some embodiments of the APS system incorporate an agitation mechanism to agitate, or message, the peritoneal cavity to promote free fluid flow within the cavity. For example, the system may include an external massager or agitator which massages or agitates the abdomen of the patient. Or, for example, the agitation may be internal, incorporated into a perfusate catheter or a separate device. The agitation may include pressurized fluid, mechanical agitation, bubbles of gas or fluid, pulsating fluid delivery and/or removal etc.

[0089] Example of Data Processing System

[0090] Fig. 10 is a block diagram of a data processing system, which may be used with any embodiment of the invention. For example, the system 1000 may be used as part of the controller. Note that while Fig. 10 illustrates various components of a computer system, it is not intended to represent any particular architecture or manner of interconnecting the components; as such details are not germane to the present invention. It will also be appreciated that network computers, handheld computers, mobile devices, tablets, cell phones and other data processing systems which have fewer components or perhaps more components may also be used with the present invention.

[0091] As shown in Fig. 10, the computer system 1000, which is a form of a data processing system, includes a bus or interconnect 1002 which is coupled to one or more microprocessors 1003 and a ROM 1007, a volatile RAM 1005, and a non-volatile memory 1006. The microprocessor 1003 is coupled to cache memory 1004. The bus 1002 interconnects these various components together and also interconnects these components 1003, 1007, 1005, and 1006 to a display controller and display device 1008, as well as to input/output (I/O) devices 1010, which may be mice, keyboards, modems, network interfaces, printers, and other devices which are well-known in the art.

[0092] Typically, the input/output devices 1010 are coupled to the system through input/output controllers 1009. The volatile RAM 1005 is typically implemented as dynamic RAM (DRAM) which requires power continuously in order to refresh or maintain the data in the memory. The non-volatile memory 1006 is typically a magnetic hard drive, a magnetic optical drive, an optical drive, or a DVD RAM or other type of memory system which maintains data even after power is removed from the system. Typically, the non-volatile memory will also be a random access memory, although this is not required.

[0093] While Fig. 10 shows that the non-volatile memory is a local device coupled directly to the rest of the components in the data processing system, the present invention may utilize a non-volatile memory which is remote from the system; such as, a network storage device which is coupled to the data processing system through a network interface such as a modem or Ethernet interface. The bus 1002 may include one or more buses connected to each other through various bridges, controllers, and/or adapters, as is well-known in the art. In one embodiment, the I/O controller 1009 includes a USB (Universal Serial Bus) adapter for controlling USB peripherals. Alternatively, I/O controller 1009 may include IEEE-594 adapter, also known as FireWire adapter, for controlling FireWire devices, SPI (serial peripheral interface), I2C (inter-integrated circuit) or UART (universal asynchronous receiver/transmitter), or any other suitable technology. Wireless communication protocols may include Wi-Fi, Bluetooth, ZigBee, near-field, cellular and other protocols.

[0094] Some portions of the preceding detailed descriptions have been presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory. These algorithmic descriptions and representations are the ways used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art. An algorithm is here, and generally, conceived to be a self-consistent sequence of operations leading to a desired result. The operations are those requiring physical manipulations of physical quantities.

[0095] It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities. Unless specifically stated otherwise as apparent from the above discussion, it is appreciated that throughout the description, discussions utilizing terms such as those set forth in the claims below, refer to the action and processes of a computer system, or similar electronic computing device, that manipulates and transforms data represented as physical (electronic) quantities within the computer system's registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage, transmission or display devices.

[0096] The techniques shown in the figures can be implemented using code and data stored and executed on one or more electronic devices. Such electronic devices store and communicate (internally and/or with other electronic devices over a network) code and data using computer-readable media, such as non-transitory computer-readable storage media (e.g., magnetic disks; optical disks; random access memory; read only memory; flash memory devices; phase-change memory) and transitory computer-readable transmission media (e.g., electrical, optical, acoustical or other form of propagated signals— such as carrier waves, infrared signals, digital signals).

[0097] The processes or methods depicted in the preceding figures may be performed by processing logic that comprises hardware (e.g. circuitry, dedicated logic, etc.), firmware, software (e.g., embodied on a non-transitory computer readable medium), or a combination of both. Although the processes or methods are described above in terms of some sequential operations, it should be appreciated that some of the operations described may be performed in a different order. Moreover, some operations may be performed in parallel rather than sequentially.

[0098] From the foregoing, it will be appreciated that specific embodiments of the invention have been described herein for purposes of illustration, but that various modifications may be made without deviating from the spirit and scope of the various embodiments of the invention. For example, several embodiments may include various suitable combinations of components, devices and/or systems from any of the embodiments described herein. Further, while various advantages associated with certain embodiments of the invention have been described above in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the invention.

[0099] The foregoing description of various embodiments of the invention has been presented for purposes of illustration and description. It is not intended to limit the invention to the precise forms disclosed. Many modifications, variations and refinements will be apparent to practitioners skilled in the art. For example, embodiments of the apparatus and related methods can be configured for performing hypothermic treatments at a number of access points in the body including the abdominal, thoracic, spinal and cerebral regions. Embodiments of the apparatus can also be sized or otherwise adapted for pediatric and neonatal applications.

[0100] Elements, characteristics, or acts from one embodiment can be readily recombined or substituted with one or more elements, characteristics or acts from other embodiments to form numerous additional embodiments within the scope of the invention. Moreover, elements that are shown or described as being combined with other elements, can, in various embodiments, exist as standalone elements. Hence, the scope of the present invention is not limited to the specifics of the described embodiments, but is instead limited solely by the appended claims.

Claims

CLAIMS What is claimed is:

1. A perfusion system, comprising:

a fluid source for perfusing a fluid within a body cavity of a subject, wherein the fluid source has a pH level of at least 8;

a catheter defining a distal opening and at least one lumen which is in fluid communication with the fluid source; and

a fluid waste reservoir for receiving the fluid from the body cavity.

2. The system of claim 1 wherein the catheter defines a second lumen which is in fluid communication with the fluid waste reservoir.

3. The system of claim 1 further comprising a second catheter separate from the catheter and which is in fluid communication with the fluid waste reservoir.

4. The system of claim 1 further comprising a pump in fluid communication with the at least one lumen.

5. The system of claim 1 wherein the pH of the fluid source is sufficient to reduce a level of C0₂ within tissue contacted by the fluid within the body cavity.

6. The system of claim 1 further comprising a controller in communication with the catheter and configured to control perfusion of the fluid within the body cavity.

7. The system of claim 6 further comprising at least one sensor in communication with the controller, wherein the at least one sensor is configured to sense one or more physiological parameters from the subject.

8. The system of claim 7 wherein the controller is further configured to adjust a parameter of the fluid in response to the one or more physiological parameters sensed from the subject.

9. The system of claim 1 wherein the controller is further configured to increase an 0₂ level of the subject

10. The system of claim 1 wherein the controller is further configured to adjust one or more parameters of the fluid source.

11. The system of claim 1 further comprising an agitation mechanism configured to agitate the fluid within the body cavity.

12. The system of claim 11 wherein the agitation mechanism is positionable externally of the body cavity and configured to contact an abdomen of the patient.

13. The system of claim 11 wherein the agitation mechanism is integrated within the catheter.

14. The system of claim 1 further comprising a mechanism positioned in proximity to the distal opening of the catheter and configured to maintain the distal opening at a distance from a tissue surface.

15. The system of claim 14 wherein the mechanism comprises a structure defining a plurality of openings which permit the fluid to flow unhindered relative to the distal opening.

16. The system of claim 1 wherein the fluid source has a pH level of at least 9.

17. The system of claim 1 wherein the fluid source has a pH level of at least 10.

18. A method of perfusing a body cavity of a subject, comprising: perfusing a fluid from a fluid source and into the body cavity through a catheter which defines a distal opening and at least one lumen which is in fluid communication with the fluid source, wherein the fluid has a pH level of a least 8;

reducing an accumulation of C0₂ within the subject via the perfused fluid; and receiving the fluid from the body cavity and into a fluid waste reservoir.

19. The method of claim 18 wherein receiving the fluid from the body cavity comprises receiving the fluid through a second lumen defined through the catheter and into the fluid waste reservoir.

20. The method of claim 18 wherein receiving the fluid from the body cavity comprises receiving the fluid through a second catheter and into the fluid waste reservoir.

21. The method of claim 18 wherein perfusing the fluid comprises perfusing via a pump in fluid communication with the at least one lumen.

22. The method of claim 18 wherein perfusing the fluid comprises perfusing the fluid into a peritoneal cavity of the subject.

23. The method of claim 18 wherein reducing the accumulation of C0₂ comprises reducing the accumulation within tissue contacted by the fluid.

24. The method of claim 18 wherein perfusing the fluid comprises adjusting a flow of the fluid via a controller in communication with the catheter.

25. The method of claim 18 wherein reducing the accumulation comprises adjusting a flow of the fluid via a controller in communication with the catheter.

26. The method of claim 18 further comprising sensing one or more physiological parameters from the subject via at least one sensor in communication with a controller.

27. The method of claim 26 further comprising adjusting a parameter of the fluid in response to the one or more physiological parameters sensed from the subject.

28. The method of claim 18 further comprising increasing an 0₂ level of the subject independently from reducing the accumulation of C0₂.

29. The method of claim 18 wherein reducing the accumulation comprises adjusting one or more parameters of the fluid source.

30. The method of claim 18 further comprising agitating the fluid within the body cavity.

31. The method of claim 30 wherein agitating the fluid comprises contacting an external region of the body cavity to agitate the fluid within the body cavity.

32. The method of claim 30 wherein agitating the fluid comprises agitating the fluid via a mechanism integrated with the catheter.

33. The method of claim 18 further comprising maintaining a distance between the distal opening of the catheter from a tissue surface such that the fluid flows unhindered relative to the distal opening.

34. The method of claim 18 wherein the fluid has a pH level of at least 9.

35. The method of claim 18 wherein the fluid has a pH level of at least 10.