IMPLANTABLE PUMP SYSTEM ENHANCEMENTS FOR USE IN CONDUCTNG DIRECT SODIUM REMOVAL THERAPY

Enhanced systems and methods for performing Direct Sodium Removal (DSR) therapy are provided in which an implantable device includes a variable speed motor-driven pump that may be programmed to output different flow rates at different stages of a DSR therapy session, wherein the system monitors operational parameters of the pump and is configured to generate an alarm condition indicative of a fault that may be displayed on a patient's smartphone to permit corrective action, and in which a catheter set implanted with the implantable device enables a DSR solution may be instilled into the patient's peritoneal cavity using a peritoneal catheter that is subsequently used to remove the DSR solution and sodium-rich ultrafiltrate from the peritoneal cavity to the patient's bladder.

FIELD OF THE INVENTION

The present invention relates generally to an enhanced implantable pump system for use in conducting direct sodium removal therapy in patients afflicted with heart failure or cardio-renal disease, and methods of use, in which a no or low sodium infusate is instilled into a patient's peritoneal cavity, and after a dwell time, the remaining infusate and accumulated ultrafiltrate and sodium is pumped to the patient's bladder using an implantable pump system.

BACKGROUND

Patients afflicted with diverse forms of heart failure and/or cardio-renal disease are prone to the accumulation of additional sodium in body tissues and increased fluid retention. For example, in congestive heart failure, due to dysfunction of the left side or right side of the heart, or both, the body is unable to pump blood with normal efficiency, leading to the reduction of blood pressure in systemic circulation. In an attempt to increase blood pressure, the body retains sodium (and water), which leads to stasis or pooling of blood or fluid in the lungs or liver, edema and/or cardiac hypertrophy.

Methods, systems and compositions for directly removing excess sodium and water using a no or low sodium infusate instilled into a patient's peritoneal cavity are described in commonly-assigned U.S. Pat. No. 10,918,778, the entirety of which is hereby incorporated by reference. That patent describes a battery-powered pump, designed to be implanted subcutaneously, that includes an inlet catheter configured to be disposed within a patient's peritoneal cavity and an output catheter configured to be coupled to the patient's bladder. The pump is programmed to periodically actuate to move fluid from the peritoneal cavity to the bladder, where the fluid may be voided during urination.

As described in the above-incorporated patent, Direct Sodium Removal (“DSR”) Therapy may be conducted periodically, e.g., daily or once weekly, to remove excess sodium and fluid from a patient to reduce fluid-overload, edema, and to reduce cardiac effort in patients with heart failure, such as Heart Failure with reduced Ejection Fraction (“HFrEF”). To conduct such therapy, a quantity, e.g., up to 2 liters, of a no or low sodium DSR solution is instilled into the patient's peritoneal cavity for a dwell period, which may vary from a couple of hours up to 24 hours, depending on type of DSR infusate used. During the dwell period, the DSR solution creates a sodium gradient that draws excess sodium from the patient's tissues and/or bloodstream into the peritoneal cavity, along with a corresponding volume of ultrafiltrate, e.g., water. At the conclusion of the dwell period, the implantable pump is actuated to move the now sodium-rich DSR solution and ultrafiltrate from the peritoneal cavity to the bladder. As observed in the above-incorporated patent and in initial human clinical testing, DSR therapy can reduce physiologically significant amounts of sodium and fluid from the patient, thereby reducing fluid overload and improving cardiac function.

One aspect of DSR therapy, as described in the above patent, is that the dwell period for the DSR solution in the patient's peritoneal cavity may be based on the physician's prior clinical experience and assessment of the specific patient's physiology. In the above incorporated, commonly assigned, U.S. patent application Ser. No. 17/650,183, in one aspect of that invention an analyte sensor is described as associated with the implantable pump system for monitoring an analyte concentration, such as sodium ions, in the fluid in the patient's peritoneal cavity, and for automatically adjusting the dwell time prior to initiating fluid transfer to the patient's bladder to adapt the general DSR therapy to the physiologic needs of specific patients. For example, some patients may have a high level of excess sodium stored in extravascular spaces, e.g., in interstitial spaces and tissues, whereas others may not. Consequently, the above-incorporated application discloses adjusting a dwell period for a DSR solution in accordance with a monitored analyte concentration, or to transfer a specified amount of analyte from the peritoneal cavity to the bladder for a particular therapy session.

One feature of the implantable pump of the above-incorporated application is that the pump generally is operated at a substantially constant motor speed during actuation. In may occur, however, depending upon the specific patient's physiology and the type of DSR solution used, that fluid or sodium accumulation in the patient's peritoneal cavity may progress faster than anticipated by the physician. In such a case, it may be desirable to provide an implantable system with a variable motor speed, which may be adjusted manually or on a pre-programmed basis to pump fluid from the patient's peritoneal cavity at different flow rates during or subsequent to the DSR therapy session. For example, it may be desirable to accelerate fluid transfer to substantially empty the bulk of the instilled fluid and ultrafiltrate promptly after expiration of a nominal dwell time (or as indicated responsive to monitored analyte concentration) and then employ a lower pump speed to transfer subsequently accumulated fluid.

In connection with enabling variable pumping speeds, as mentioned above, it further would be desirable to provide a more robust alarm system for the implantable pump system. For example, whereas the implantable pump described in the above-identified patent employed a single flow rate, with the additional of multiple flow rates as discussed in the preceding paragraph, it would be desirable to monitor the pump speed to ensure that a desired pump speed is attained during a specified interval. If the desired pump speed is not attained, for example, due to proteinaceous buildup within the pump, it would be desirable for the processor controlling the implantable pump to generate an alarm that is communicated to the patient, e.g., via the external charging system or by communication with software loaded onto a patient's smartphone. The patient might then be presented with various options for rectifying the alarm condition.

In addition, the implantable pump system described in the above-identified patent included pressure sensors for monitoring intraabdominal pressure, and activating the implantable pump when the pressure exceeds a specified threshold value. In the context of DSR therapy, however, in view of the compliance of the abdominal cavity, it instead may be desirable to monitor and trigger pump actuation based on the time-dependent evolution of pressure within the peritoneal cavity. In this manner, the implantable pump could differentiate between pressure fluctuations caused by the patient coughing or bending over from pressure increases resulting from filling of the peritoneal cavity.

It also may be desirable to employ the catheter used for instilling the DSR fluid into the patient's peritoneal cavity during initiation of the DSR therapy to flush potential blockages from the inlet of the implantable pump.

Accordingly, it would be desirable to develop provide an implantable pump system for use in conducting DSR therapy sessions in which the implantable pump system provides additional flexibility in ease of use as well as enhanced monitoring and safety features.

SUMMARY OF THE INVENTION

The present invention is directed to an implantable pump system having enhanced features and programming adapted for conducting DSR therapy for patients suffering from fluid and/or sodium overload, e.g., heart failure patients and patients afflicted with cardio-renal disease. In accordance with one aspect of the invention, an implantable pump system as described in commonly assigned U.S. Pat. No. 10,918,778 and/or U.S. patent application Ser. No. 17/650,183 is provided, which in addition provides additional enhancements for use in conducting DSR therapy, including variable programmable pump speeds, a set of more comprehensive set of alarm conditions and trouble-shooting options for resolving such alarm conditions, and increases ease of use for instilling a DSR solution during initiation of the DSR therapy.

In accordance with the principles of the present invention, an implantable pump system is provided that includes a programmable variable-speed implantable pump coupled to an inlet catheter having an inlet end configured to be disposed in a patient's peritoneal cavity and an outlet catheter having an outlet end configured to be disposed in the patient's bladder. The implantable pump is configured for wireless communication with an external charging and communication system. The external charging and communication system in turn may be configured to communicate with a software application installed on a physician monitoring and control system and optionally, a software application installed on the patient's smartphone, personal computer or tablet. In one preferred embodiment, such as described in the above-incorporated application, the implantable pump system includes sensor for measuring a concentration of an analyte, such as sodium, for detecting a concentration of an infusate component, such as dextrose or icodextrin, or an osmotic pressure or gradient, or for monitoring an amount of sodium removed from the peritoneal cavity to the bladder during a pumping session.

Further in accordance with the principles of the invention, the implantable pump includes a positive-displacement gear pump, such that the volume of fluid transferred during a pumping session may be accurately computed based on the number of gear rotations during a specified interval. According to one aspect of the invention, the implantable pump system includes an on-board processor that may be programmed by the patient's physician to operate the gear pump at different speeds. For example, the pump may operate at a first speed to rapidly transfer fluid from a patient's peritoneal cavity to the patient's bladder following completion of a predetermined dwell time, or in response to detection by the analyte sensor of an analyte level in the peritoneal cavity above a predetermined threshold. The implantable pump also may be programmed to operate thereafter at a substantially lower speed to periodically remove further fluid accumulations from the peritoneal cavity after the conclusion of the DSR therapy session. Further, the implantable pump may be operated at a selected speed specifically in response to a command transmitted by the patient, his or her caretaker or physician.

In accordance with another aspect of the invention, the implantable pump system includes an enhanced alarm monitoring and notification capability. In particular, to address the increased pump speed programming complexity, the implantable pump system preferably includes additional alarm monitoring, reporting and resolution capability. For example, a preferred embodiment may include programming for monitoring pump operation that promptly generates an alarm to notify the patient, via the external charging and control system or a smartphone application, that the pump output is below a specified threshold for output for a particular phase of the DSR session. In this case, the patient may be contact his or her physician, who may send commands via the smartphone application to the implantable pump system to increase pump speed for the remainder of the pumping session. Alternatively, if the alarm identifies a blockage in the gear pump due to the presence of particulate matter, the programming may notify the patient to request that the physician remotely activate a boost mode or jog mode to overcome and/or grind and remove the obstruction, as described below. Alternatively, the smartphone application may send such notifications directly to the patient's physician, as well as the patient. In a still further alternative embodiment, the alarm software of the implantable pump system may monitor intraabdominal pressure during instillation of the DSR fluid or during the dwell period, and notify the patient to request cessation of addition of DSR fluid to the peritoneal cavity or to prompt transfer of accumulated fluid to the patient's bladder.

In yet another aspect of the invention, the implantable pump system may include advanced algorithms for determining completion of a dwell period and when to activate the pump to transfer fluid from the peritoneal cavity to the bladder. The above-incorporated patent and application describe that the dwell period for retaining the DSR solution in the peritoneal cavity may be based on a specified time, e.g., 2 hours, attaining a threshold intraabdominal pressure, or attaining an analyte concentration level in the fluid in peritoneal cavity. In accordance with the present invention, actuation of the implantable pump further may be triggered by monitoring the rate of change of pressure within the peritoneal cavity over a specified time interval. In this manner, the pump will not be inadvertently triggered by transient increases in intraabdominal pressure, e.g., due to patient coughing or transient postural changes.

Further in accordance with the principles of the invention, the implantable pump system may include an improved fluid transfer set for flushing the peritoneal catheter when instilling DSR fluid into the patient's peritoneal cavity during initiation of the DSR session. In one preferred embodiment, the inlet catheter to the pump includes a tee-shaped junction, wherein a first side of the junction has an instillation line configured to be coupled to a subcutaneous port having a self-healing membrane, a second side of the junction couples to a peritoneal catheter configured to be positioned in the peritoneal cavity and a third port of the junction is configured to be coupled via tubing to the implantable pump inlet port. A valve optionally may be incorporated into the tee-shaped junction, which closes to prevent instilled fluid from flowing into the implantable pump during infusion of DSR solution, and which closes the instillation during pumping of fluid from the peritoneal cavity to the bladder.

In this manner, DSR solution, typically 0.5 up to 2 liters, may be instilled via a needle inserted into the subcutaneous port, so that it flows through the instillation line, the tee junction with optional valve and the peritoneal catheter into the peritoneal cavity, thereby flushing the peritoneal catheter of any debris. After instillation of the DSR solution is completed, the needle is withdrawn. Upon completion of the dwell period, as may be determined by expiration of a specified time, analyte concentration, or rate of change of intraabdominal pressure, the implantable pump is actuated so that fluid is withdrawn from the peritoneal cavity via the peritoneal catheter, the tee junction and the inlet catheter to the implantable pump. No fluid is drawn through the instillation line as the self-healing membrane on the subcutaneous port and valve, if present, will seal the instillation line. In this manner, the peritoneal catheter may be used to rapidly deliver DSR fluid into the peritoneal cavity while ensuring that the catheter remains free of blockage.

In an alternative embodiment, the improved fluid transfer set for instilling DSR fluid into the patient's peritoneal cavity during initiation of the DSR session may include a Y-shaped connector that may be assembled with the peritoneal catheter during implantation of the implantable device.

Other features of the inventive system and methods will be apparent with reference to the following description and figures.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to system and methods for conducting direct sodium removal (“DSR”) therapy using compositions as described in above-incorporated U.S. Pat. No. 10,918,778 and U.S. patent application Ser. No. 17/661,737. As described in that patent and pending application, DSR therapy may be used to treat fluid overload in various forms of heart failure and renal disease. In accordance with the principles of the present invention, enhanced systems and methods are provided for conducting DSR therapy in an implantable pump is employed to instill DSR solution into the patient's peritoneal cavity, monitor ultrafiltrate and sodium accumulation in the peritoneal cavity and remove such accumulations to the patient's bladder. The enhanced implantable pump may include variable programmable pumping speeds, one or more alarms for alerting the patient of potential pump blockages or malfunction, and selectable options for correcting reported alarm conditions. The implantable pump further may include programming for assessing the progress of the DSR therapy session, and for monitoring pressure fluctuations with the peritoneal cavity, which may serve as triggers for actuating the pump to move sodium-laden DSR solution and ultrafiltrate from the peritoneal cavity to the patient's bladder. In addition, the enhanced implantable pump system may include catheter sets configured to facilitate infusion and removal of DSR infusate into the patient's peritoneal cavity.

As described in the above-incorporate patent and application, the no or low sodium concentration in the DSR solution is configured to cause sodium and fluid (osmotic ultrafiltrate) to pass from the patient's body into the peritoneal cavity. As used in this disclosure, a no or low sodium DSR solution has a sodium content of less than 120 meq/L, more preferably, less than 35 meq/L, and includes infusates having virtually zero concentration of sodium. Accordingly, the methods of the present invention specifically contemplate use of the inventive system to monitor the presence of fluid accumulated in the peritoneal cavity, along with sodium, and to trigger actuation of the pump to move the ultrafiltrate and sodium to the patient's bladder for subsequent voiding via urination.

Exemplary DSR solution formulations presented in the incorporated patent and application include one or more solutions including: D-0.5 to D-50 solutions, i.e., from 0.5 to 50 grams of dextrose per 100 ml of aqueous solution; Icodextrin or dextrin solutions having from 0.5 to 50 grams of icodextrin/dextrin per 100 ml of aqueous solution; urea, and high molecular weight glucose polymer solutions (weight average molecular weight Da>10,000) having from 0.5 to 50 grams of high molecular weight glucose polymer per 100 ml of aqueous solution, and combinations thereof. The aqueous solution includes at least purified water, and may in addition include electrolytes such as low amounts of magnesium or calcium salts, preservatives, ingredients having antimicrobial or antifungal properties, or buffering materials to control pH of the infusate. Icodextrin, a high molecular weight glucose polymer, or other high molecular weight glucose polymer (weight average molecular weight, Da>10,000,) is preferable because it experiences a lower rate of uptake when employed in peritoneal dialysis, and thus lower impact on serum glucose concentrations compared to a dextrose-based solutions.

Overview of an Exemplary System of the Present Invention

Referring toFIG.1, exemplary system10of the present invention is described. InFIG.1, components of the system are not depicted to scale on either a relative or absolute basis. System10comprises implantable device20, external charging and communication system30, software-based monitoring and control system40, and optionally, smartphone or tablet50. In the illustrated embodiment, monitoring and control system40is configured to be installed and run on a conventional laptop computer, tablet or smartphone, as may be used by the patient's physician. During patient visits, charging and communication system30may be coupled, either wirelessly or using a cable, to monitoring and control system40to download for review data stored on implantable device20, or to adjust the operational parameters of the implantable device. Monitoring and control system40also may be configured to upload and store date retrieved from charging and communication system30to a remote server for later access by the physician or charging and communications system30. Smartphone or tablet50may comprise, for example, the patient's personal smartphone having application software that forms a subset of the capabilities of the software of monitoring and control system40. In particular, smartphone50may include an application configured to communicate with implantable device20, either directly or through external charging and communication system30, to present alarms to the patient and permit the patient to issue a limited number of claims directly to the implantable device20.

Implantable device20comprises an electromechanical pump having housing21configured for subcutaneous implantation. Implantable device20may include an electrically-driven mechanical gear pump and connectors22and24configured to reduce the risk of improper installation and inadvertent disconnection. Bladder catheter25is coupled to pump housing21using connector24. Peritoneal catheter23is coupled to pump housing21using connector22. Peritoneal catheter23has a proximal end configured to be coupled to pump housing21and a distal end configured to be positioned in the peritoneal cavity. Bladder catheter25has a proximal end configured to be coupled to pump housing21and a distal end configured to be inserted through the wall of, and fixed within, a patient's bladder. In a preferred embodiment, both catheters are made of medical-grade silicone and include polyester cuffs at their distal ends (not shown) to maintain the catheters in position.

In a preferred embodiment, implantable device20includes pressure sensors that monitor pressure in one or both of the peritoneal cavity and the bladder. Implantable device20may include at least one analyte sensor for generating an output signal corresponding to concentration of a predetermined analyte, such as sodium, or a concentration of an infusate component, such as dextrose or icodextrin. In this manner, movement of sodium-laden DSR solution and ultrafiltrate fluid from the peritoneal cavity to the bladder may be controlled in accordance with one or more target analyte concentrations determined by the physician. In addition, the output of the pressure sensors may cause pumping of fluid into the bladder to be disabled if the bladder pressure reaches a level indicating insufficient space for the bladder to accommodate additional fluid or if the pressure in the peritoneal cavity falls below preset threshold.

In accordance with one aspect of the invention, implantable device20may include a variable speed gear pump that may be programmed to pump at different speeds at different times during a DSR therapy session. For example, the implantable pump may be programmed to operate at a first speed to rapidly transfer fluid from a patient's peritoneal cavity to the patient's bladder following completion of a predetermined dwell time or in response to a detected analyte concentration exceeding a predetermined threshold. The implantable pump further may be programmed thereafter to operate at a substantially lower speed to periodically remove further fluid accumulations from the peritoneal cavity during later intervals of, or after the conclusion of, the DSR therapy session. Further, the implantable pump may be operated at a selected speed specifically in response to a command transmitted by the patient, his or her caretaker or physician at specific times during the DSR therapy session or thereafter. Implantable device20preferably includes multiple separate fail-safe mechanisms, to ensure that urine cannot pass from the bladder to the peritoneal cavity through the pump, thereby reducing the risk of transmitting infection.

In accordance with another aspect of the invention, the implantable pump system may include an enhanced alarm monitoring and notification capability. In particular, to address the increased pump speed programming complexity, the implantable pump system may include enhanced alarm monitoring, reporting and resolution capability. For example, in one embodiment, the implantable device may include programming for monitoring pump operation and generating an alarm to notify the patient, e.g., via external charging and control system30or directly via an application on smartphone50, that the pump output is below a specified threshold for output for a particular phase of the DSR session. In this case, the patient may be directed to contact his or her physician to request that pump speed be increased for the remainder of the pumping session. Alternatively, if the alarm indicates a blockage in the gear pump, e.g., due to the presence of particulate matter, the alarm transmitted to the patient via smartphone50may prompt the patient to activate, or request the physician to activate, a boost mode or jog mode to overcome and/or grind and remove the obstruction, as described below. Still further, the implantable pump may include software that sends an alarm to smartphone50if the monitored intraabdominal pressure exceeds a preset threshold during instillation of the DSR fluid or during the dwell period. In this case, the patient may request the physician to cease instillation of further DSR fluid into the peritoneal cavity or to transfer fluid accumulated fluid to the peritoneal cavity to the patient's bladder to resolve the alarm condition. Alternatively, the physician may enable smartphone50to permit the patient to make such changes in accordance with the physician's oral directions.

In yet another aspect of the invention, the implantable pump system may include advanced algorithms for determining completion of a dwell period and when to activate the pump to transfer fluid from the peritoneal cavity to the bladder. For example, the above-incorporated patent and application describe that the dwell period for retaining the DSR solution in the peritoneal cavity may be based on a specified time, e.g., 2 hours, attaining a threshold intraabdominal pressure, or attaining an analyte concentration level in the fluid in peritoneal cavity. In accordance with the present invention, actuation of the implantable pump further may be triggered by monitoring the rate of change of pressure within the peritoneal cavity over a specified time interval. In this manner, the pump will not be inadvertently triggered by transient fluctuations in intraabdominal pressure, e.g., due to patient coughing or transient postural changes. Instead, the implantable pump will begin transferring fluid from the peritoneal cavity to the bladder only after a sustained increase in pressure exceeding a predetermined threshold is detected.

Still referring toFIG.1, external charging and communication system30of the exemplary system, preferably includes base31and handpiece32. Handpiece32may contain a controller, a radio transceiver, an inductive charging circuit, a battery, a quality-of-charging indicator and a display, and may be removably coupled to base31to recharge the battery. Base31may contain a transformer and circuitry for converting conventional 120V or 220-240V service to a suitable DC current to charge handpiece32when coupled to base31. Alternatively, handpiece32may include such circuitry and a detachable power cord, thus permitting the handpiece to be directly plugged into a wall socket to charge the battery. Preferably, each of implantable device20and handpiece32includes a device identifier stored in memory, such that handpiece32provided to the patient is coded to operate only with that patient's specific implantable device20.

Handpiece32illustratively includes housing33having multi-function button34, display35, a plurality of light emitting diodes (LEDs, not shown) and inductive coil portion36. Multi-function button34enables the patient to issue a limited number of commands to implantable device20, while display35provides visible confirmation that a desired command has been input; it also may display battery status of implantable device20. Inductive coil portion36houses an inductive coil that is used transfer energy from handpiece32to recharge the battery of implantable device20. The LEDs, which are visible through the material of housing33when lit, may be arranged in three rows of two LEDs each, and are coupled to the control circuitry and inductive charging circuit contained within handpiece32. The LEDs may be arranged to light up to reflect the degree of inductive coupling achieved between handpiece32and implantable device20during recharging of the latter. Alternatively, the LEDs may be omitted and an analog display provided on display35indicating the quality of inductive coupling.

Control circuitry contained within handpiece32is coupled to the inductive charging circuit, battery, LEDs and radio transceiver, and includes memory for storing information received from implantable device20. Handpiece32also preferably includes a data port, such as a USB port, that permits the handpiece to be coupled to monitoring and control system40during visits by the patient to the physician's office. Alternatively, handpiece32may include a wireless chip, e.g., that conforms to the Bluetooth or IEEE 802.11 wireless standards, thereby enabling the handpiece to communicate wirelessly with monitoring and control system40, either directly or via the Internet.

External charging and communication system30also may be configured to communicate directly with smartphone50, as well as monitoring and control system40. Thus, implantable device20may be configured to communicate with smartphone50via external charging and control system30when external charging and communication system40is coupled to implantable device20, for example, when charging. Implantable device20also may be configured directly with smartphone50, for example, to communicate alarms to smartphone50and to receive commands to resolve such alarms from smartphone50. Smartphone50also may communicate alarm conditions, and the resolution of such conditions, to external charging and communication system30for storage and later reporting to monitoring and control system40.

Monitoring and control system40is intended primarily for use by the physician and comprises software configured to run on a conventional computer, e.g., a laptop as illustrated inFIG.1, or a tablet or smartphone. The software enables the physician to configure, monitor and control operation of charging and communication system30and implantable device20. The software may include routines for configuring and controlling pump operation, such as a target analyte concentration at which pumping is actuated, the amount of analyte transferred from the peritoneal cavity to the bladder during a pumping session, pumping speeds for various intervals of the dwell period and post-dwell period, a maximum dwell time for the DSR therapy, and limits on intraabdominal pressure, bladder pressure, pump pressure, and battery temperature. System40also may provide instructions to implantable device20via charging and control system30to control operation of implantable device20so as not to move fluid during specific periods (e.g., at night or when the bladder is full) or to defer pump actuation.

System40also may be configured, for example, to send immediate commands to the implantable device to start or stop the pump, or to operate the pump in reverse or at high power to unblock the pump or associated catheters, a subset of which may be available to the patient using an application installed on smartphone50. The software of system40may be configured to download real-time data relating to pump operation, as well as event logs stored during operation of implantable device20. Based on the downloaded data, e.g., based on measurements made of the patient's analyte concentration, intraabdominal pressure, respiratory rate, and/or fluid accumulation, the software of system40optionally may be configured to analyze such data to alert the physician to the development of potential trends. Such analyses may include generating alerts regarding prediction or detection of heart failure decompensation or a change in the patient's health for which an adjustment to the flow rate, volume, time and/or frequency of pump operation may be required. Finally, system40optionally may be configured to remotely receive raw or filtered operational data from handpiece32over a secure Internet channel.

The Implantable Device

Referring now toFIG.2, a schematic depicting the functional blocks of implantable device20suitable for use in practicing the methods of the present invention is described. Implantable device20includes control circuitry, illustratively processor70coupled to nonvolatile memory71, such as flash memory or electrically erasable programmable read only memory, and volatile memory72via data buses. Processor70is electrically coupled to electric motor73, battery74, inductive circuit75, radio transceiver76, one or more analyte sensors85, and a plurality of other sensors, including humidity sensor77, one or more temperature sensors78, accelerometer79, pressure sensors80, and respiratory rate sensor81. Inductive circuit75is electrically coupled to coil84to receive energy transmitted from charging and communication system30, while transceiver76is coupled to antenna82, and likewise is configured to communicate with a transceiver in charging and communication system30and smartphone50, as described below. Optionally, inductive circuit75also may be coupled to infrared light emitting diode83. Motor73may include a dedicated controller, which interprets and actuates motor73responsive to commands from processor70. All of the components depicted inFIG.2are contained within a low volume sealed biocompatible housing, depicted inFIG.3A.

Processor70executes firmware stored in nonvolatile memory71which controls operation of motor73responsive to signals generated by motor73, sensors77-81and85, and commands received from transceiver76. Processor70also controls reception and transmission of messages via transceiver76and operation of inductive circuit75to charge battery74. In addition, processor70receives signals generated by Hall Effect sensors located within motor73, which are used to compute direction and revolutions of the gears of the gear pump, and thus fluid volume transferred and the viscosity of that fluid, as described below. Processor70preferably includes a low-power mode of operation and includes an internal clock, such that the processor can be periodically awakened to handle pumping, pump tick mode, or communications and charging functions, and/or awakened to handle commands received by transceiver76from handpiece32. In one embodiment, processor70comprises a member of the MSP430 family of microcontroller units available from Texas Instruments, Incorporated, Dallas, Tex., and may incorporate the nonvolatile memory, volatile memory, and radio transceiver components depicted inFIG.2. In addition, the firmware executed on processor70may be configured to respond directly to commands sent to implantable device20via charging and communication system30. Processor70also is configured to monitor operation of motor72(and any associated motor controller) and sensors77-81and85, as described below, and to store data reflecting operation of the implantable device, including event logs, and to generate alarms corresponding to various fault conditions. Such stored data and alarms may be reported to the charging and communication system when it is next wirelessly coupled to the implantable device, while alarms also may be communicated to smartphone50. In a preferred embodiment, processor70generates up to eighty log entries per second prior to activating the pump, about eight log entries per second when the implantable system is actively transferring fluid and about one log entry per hour when not transferring fluid. As discussed above, processor70may be programmed to operate motor73at variable speeds responsive to stored programming or commands received directly via external charging and communication system30or smartphone50.

Nonvolatile memory71preferably comprises flash memory or EEPROM, and stores a unique device identifier for implantable device20, firmware to be executed on processor70, configuration set point data relating to operation of the implantable device, and optionally, coding to be executed on transceiver76and/or inductive circuit75, and a separate motor controller, if present. Firmware and set point data stored on nonvolatile memory71may be updated using new instructions provided by control and monitoring system40via charging and communication system30. Volatile memory72is coupled to and supports operation of processor70, and stores data and event log information gathered during operation of implantable device20. Volatile memory72also serves as a buffer for communications sent to, and received from, charging and communication system30and smartphone50.

Transceiver76preferably comprises a radio frequency transceiver and is configured for bi-directional communications via antenna76with a similar transceiver circuit disposed in handpiece32of charging and communication system30. Transceiver76may include a communications circuit, e.g., near field or Bluetooth, for directly communicating in a bi-directional manner with an application program loaded on smartphone50. Transceiver76also may include a low power mode of operation, such that it periodically awakens to listen for incoming messages and responds only to those messages that include the unique device identifier assigned to that implantable device. Alternatively, transceiver76may be configured to send or receive data to external charging and communications system30only when inductive circuit75of the implantable device is active. Transceiver76may employ an encryption routine to ensure that messages sent from, or received by, the implantable device cannot be intercepted or forged.

Inductive circuit75is coupled to coil84, and is configured to recharge battery74of the implantable device when exposed to a magnetic field applied by a corresponding inductive circuit within handpiece32of charging and communication system30. In one embodiment, inductive circuit75is coupled to optional infrared LED83that emits an infrared signal when inductive circuit75is active. The infrared signal may be received by handpiece32to assist in locating the handpiece relative to the implantable device, thereby improving the magnetic coupling and energy transmission.

Inductive circuit75optionally may be configured not only to recharge battery74, but to directly provide energy to motor73in a “boost” mode or jog/shake mode to unblock the pump, for example, in response to a command issued by smartphone50. In particular, if processor70detects that motor73is stalled, e.g., due to a block created by fibrin or other debris in the peritoneal cavity, an alarm may be generated and sent to smartphone50. When the alarm is reported to smartphone50, and the patient may issue a command to processor70to apply an overvoltage to motor73from inductive circuit75for a predetermined time period to free the pump blockage. Alternatively, depressing the patient command may cause processor70to execute a set of commands by which motor73is jogged or shaken, e.g., by alternatingly running the motor in reverse and then forward, to disrupt the blockage. Because such modes of operation may employ higher energy consumption than expected during normal operation, it is advantageous to drive the motor during such procedures with energy supplied via inductive circuit75.

Battery74preferably comprises a lithium ion or lithium polymer battery capable of long lasting operation, e.g., up to three years, when implanted in a human, so as to minimize the need for re-operations to replace implantable device20. In one preferred embodiment, battery74supplies a nominal voltage of 3.6V, a capacity of 150 mAh when new, and a capacity of about 120 mAh after two years of use. Preferably, battery74is configured to supply a current of 280 mA to motor73when pumping; 25 mA when the transceiver is communicating with charging and communication system30; 8 mA when processor70and related circuitry is active, but not pumping or communicating; and 0.3 mA when the implantable device is in low power mode. More preferably, battery74should be sized to permit a minimum current of at least 450 mAh for a period of 10 seconds and 1 A for 25 milliseconds during each charging cycle.

Motor73preferably is a brushless direct current or electronically commuted motor having a splined output shaft that drives a set of floating gears that operate as a gear pump, as described below. Motor73may include a dedicated motor controller, separate from processor70, for controlling operation of the motor, and preferably is capable of operating at different speeds to achieve different fluid transfer rates. Motor73may include a plurality of Hall Effect sensors, preferably two or more, for determining motor position and direction of rotation. Due to the high humidity that may be encountered in implantable device20, processor70may include programming to operate motor73, although with reduced accuracy, even if some or all of the Hall Effect sensors fail.

In a preferred embodiment, motor73is capable of driving the gear pump to generate a nominal flow rate of 150 ml/min and applying a torque of about 1 mNm against a pressure head of 30 cm water at 3000 RPM. In this embodiment, the motor preferably is selected to drive the gears at from 1000 to 5000 RPM, corresponding to flow rates of from 50 to 260 ml/min, respectively. The motor preferably has a stall torque of at least 3 mNm at 500 mA at 3 V, and more preferably 6 mNm in order to crush non-solid proteinaceous materials. As discussed above, the motor preferably also supports a boost mode of operation, e.g., at 5 V, when powered directly through inductive circuit75. Motor73preferably also is capable of being driven in reverse as part of a jogging or shaking procedure to unblock the gear pump.

Processor70also may be programmed to automatically and periodically wake up and enter a pump tick mode. In this mode of operation, the gear pump is advanced slightly, e.g., about 120 degrees as measured by the Hall Effect sensors, before processor70returns to low power mode. Preferably, this interval is about every 20 minutes, although it may be adjusted by the physician using the monitoring and control system. Tick mode is expected to prevent the DSR solution and ultrafiltrate from partially solidifying and blocking the gear pump.

Processor70also may be programmed to enter a jog or shake mode when operating on battery power alone, to unblock the gear pump, upon receipt of a command from smartphone50or charging and communication system30. Similar to the boost mode available when charging the implantable device with the handpiece of charging and communication system30, the jog or shake mode causes the motor to rapidly alternate the gears between forward and reverse directions to crush or loosen any buildup of tissue or other debris in the gear pump or elsewhere in the fluid path. Specifically, in this mode of operation, if the motor does not start to turn within a certain time period after it is energized (e.g., 1 second), the direction of the motion is reversed for a short period of time and then reversed again to let the motor turn in the desired direction. If the motor does still not turn (e.g., because the gear pump is jammed) the direction is again reversed for a period of time (e.g., another 10 msec). If the motor still is unable to advance, the time interval between reversals of the motor direction is reduced to allow the motor to develop more power, resulting in a shaking motion of the gears. If the motor does not turn forward for more than 4 seconds, the jog mode of operation ceases, and an alarm is generated and also written to the event log. If the motor was unable to turn forward, processor70may introduce a backwards tick before the next scheduled fluid movement. A backward tick is the same as a tick (e.g., about 120 degrees forward movement of the motor shaft) but in a reverse direction, and is intended to force the motor backwards before turning forward, thus allowing the motor to gain momentum.

Sensors77-81continually monitor humidity, temperature, acceleration, pressure, and respiratory rate, and provide corresponding signals to processor70which stores the corresponding data in memory71for later transmission to monitoring and control system40. In particular, humidity sensor77is arranged to measure humidity within the housing of the implantable device, to ensure that the components of implantable device are operated within expected operational limits. Humidity sensor77preferably is capable of sensing and reporting humidity within a range or 20% to 100% with high accuracy. One or more of temperature sensors78may be disposed within the housing and monitor the temperature of the implantable device, and in particular battery74to ensure that the battery does not overheat during charging, while another one or more of temperature sensors78may be disposed so as to contact fluid entering at inlet62and thus monitor the temperature of the fluid, e.g., for use in assessing the patient's health. Accelerometer79is arranged to measure acceleration of the implant, preferably along at least two axes, to detect periods of activity and inactivity, e.g., to determine whether the patient is sleeping or to determine whether and when the patient is active. This information is provided to processor70to ensure that the pump is not operated when the patient is indisposed to attend to voiding of the bladder.

Implantable device20preferably includes multiple pressure sensors80, which are continually monitored during waking periods of the processor. As described below with respect toFIG.4A, the implantable device preferably includes four pressure sensors: a sensor to measure the pressure in the peritoneal cavity, a sensor to measure the ambient pressure, a sensor to measure the pressure at the outlet of the gear pump, and a sensor to measure the pressure in the bladder. These sensors preferably are configured to measure absolute pressure between 450 mBar and 1300 mBar while consuming less than 50 mW at 3V. Preferably, the sensors that measure pressure at the pump outlet and in the bladder are placed across a duckbill valve, which prevents reverse flow of urine and/or used DSR solution and ultrafiltrate back into the gear pump and also permits computation of flow rate based on the pressure drop across the duckbill valve.

Respiratory rate monitor81is configured to measure the patient's respiratory rate, e.g., for use in assessing the patient's health. Alternatively, the patient's respiratory rate may be measured based on the outputs of one or more of pressure sensors80, e.g., based on changes in the ambient pressure or the pressure in the peritoneal cavity caused by the diaphragm periodically compressing that cavity during breathing.

In accordance with one aspect of the present invention, analyte sensor85may be a chemical or biochemical sensor configured to monitor a sodium concentration of sodium-laden DSR solution and ultrafiltrate instilled into and accumulated within the patient's peritoneal cavity. Analyte sensor85may in addition sense a concentration of a component, such as dextrose or icodextrin concentration, in the DSR solution present in the peritoneal cavity, and that information may be used by the processor of implantable device20to trigger starting or stopping of the pump. One exemplary in vivo sensor suitable for monitoring sodium ion concentration is described in U.S. Patent Application Publication No. 2008/033260, the entirety of which is incorporated herein by reference. Analyte sensor85may be disposed on catheter23, on catheter25, or may be disposed within the housing of implantable device20so as to contact fluid flowing through the device. Any desired number of additional sensors for measuring the health of the patient also may be provided in operable communication with processor70and may output recordable parameters for storage in memory71and transmission to monitoring and control system40, that the physician may use to assess the patient's health.

In an exemplary embodiment, processor70may be programmed to monitor an output of analyte sensor85, for example, indicative of a value of sodium concentration, and to compare that value to a target sodium concentration value selected by the physician at which implantable device20is activated to transfer fluid from the peritoneal cavity to the patient's bladder. Alternatively, or in addition, analyte sensor85could measure a concentration of an infusate component remaining in the peritoneal cavity. Processor70also may be programmed to activate implantable device20to move fluid from the peritoneal cavity to the bladder after that fluid has dwelled in the peritoneal cavity a sufficient period that the measured analyte concentration exceeds or falls below a target value. In addition, fluid transfer may be initiated after infusate has dwelled in the peritoneal cavity for a predetermined maximal amount of time, which may be set by a physician. For this purpose, processor70may include a programmed timer that monitors the dwell time, e.g., elapsed time from when the DSR solution is first introduced into the patient's peritoneal cavity. As a further alternative, processor70may be programmed to compute an estimate of the amount of analyte transferred from the peritoneal cavity to the bladder as function of the measured concentration and the volume of fluid transferred, and to report that amount to the patient, physician or caretaker. Such information may, in turn, be used to determine when the next DSR therapy session should occur or be used in adjusting the volume of DSR solution to be employed during a subsequent DSR therapy session.

The volume of fluid transferred, and pump activation time and frequency may be selected to optimize sodium removal to maintain or improve the patient's health, to alleviate the fluid overload and to ensure a stable serum sodium level. These parameters may be selected based on the patient's symptoms, the activity and habits of the patient, the permeability of the peritoneal membrane and the osmotic characteristics of the DSR solution, and they may be static or changed by the physician on a session-by-session basis. For example, the physician may initially program processor70with a first sodium concentration level, amount of sodium to be removed, maximum dwell time, volume, or frequency based on his perception of the patient's health and habits, and later adjust that initial programming to vary those parameters based on his perception of changes in the patient's health, for example based on changes over time in parameters measured by implantable device20and relayed to the physician via monitoring and control software40.

Processor70also may be programmed to monitor the sensors77-81and to generate an alarm condition that is relayed to the patient and/or the clinician indicative of a potential decline in the patient's health. For example, processor70may monitor pressure sensors80to determine whether, over predetermined time intervals, there is an increase in pressure within the peritoneal cavity. Such pressure increases may be the result of an increase in the rate of accumulation of fluid in the peritoneal cavity, which may in turn indicate heart failure decompensation. Such alarm condition may inform the patient to seek immediate treatment.

Processor70further may be programmed to pump fluid from the peritoneal cavity to the bladder only when the pressure in the peritoneal cavity exceeds a first predetermined value, and the pressure in the bladder is less than a second predetermined value, so that the bladder does not become overfull. To account for patient travel from a location at sea level to a higher altitude, the ambient pressure measurement may be used to calculate a differential value for the peritoneal pressure. In this way, the predetermined pressure at which the pump begins operation may be reduced, to account for lower atmospheric pressure. Likewise, the ambient pressure may be used to adjust the predetermined value for bladder pressure. In this way, the threshold pressure at which the pumping ceases may be reduced, because the patient may experience discomfort at a lower bladder pressure when at a high altitude location.

As yet another alternative, processor70may be programmed to monitor intraabdominal pressure over a specified interval, e.g., one to three minutes or more, and to activate the implantable pump only when the pressure exceeds a specified threshold value for the specified interval. In particular, because the abdominal cavity is compliant, it may be desirable to monitor and trigger pump actuation based on the time-dependent evolution of pressure within the peritoneal cavity. In this manner, the implantable pump could differentiate between short-duration pressure fluctuations, e.g., caused by the patient coughing or bending over, from pressure increases resulting from filling of the peritoneal cavity due to ultrafiltrate accumulation.

Further, processor70may be programmed to permit transfer of fluid from the peritoneal cavity to the bladder to be interrupted, for example if the bladder pressure indicates that the bladder is full, and to resume transferring fluid once the bladder pressure sensor detects that the bladder has been voided. In this case, because the sodium concentration level may fall due to fluid transfer immediately before the bladder was detected to be full, the processor may be programmed to resume fluid transfer once the sodium concentration level has reached the target level during a single DSR therapy session.

Optionally, implantable device20may include a UV lamp (not shown) disposed in operable communication with controller70. The UV lamp may be configured to irradiate and thus kill pathogens in the DSR solution before is instilled into and/or after fluid is extracted from the peritoneal cavity. The UV lamp preferably generates light in the UV-C spectral range (about 200-280 nm), particularly in the range of about 250-265 nm, which is also referred to as the “germicidal spectrum” because light in that spectral range breaks down nucleic acids in the DNA of microorganisms. Low-pressure mercury lamps have an emission peak at approximately 253.7 nm, and may suitably be used for UV lamp85. Alternatively, the UV lamp may be a UV light emitting diode (LED), which may be based on AlGaAs or GaN.

Referring now toFIGS.3A and3B, further details of an exemplary embodiment of implantable device20are provided. InFIG.3A, housing91appears transparent, although it should of course be understood that housing91comprises an opaque biocompatible plastic, glass and/or metal alloy materials. InFIG.3B, the implantable device is shown with lower portion92of housing91removed from upper housing93and without a glass bead/epoxy filler material that is used to prevent moisture from accumulating in the device. InFIGS.3A and3B, motor94is coupled to gear pump housing95, which is described in greater detail with respect toFIG.4A. The electronic components discussed above with respect toFIG.2are disposed on circuit board substrate96, which extends around and is fastened to support member97. Coil98(corresponding to coil84ofFIG.2) is disposed on flap99of the substrate and is coupled to the electronic components on flap100by flexible cable portion101. Support member97is fastened to upper housing93and provides a cavity that holds battery102(corresponding to battery74ofFIG.2). Lower portion92of housing91includes port103for injecting the glass bead/epoxy mixture after upper portion93and lower portion92of housing91are fastened together, to reduce space in the housing in which moisture can accumulate.

Housing91also may include features designed to reduce movement of the implantable pump once implanted within a patient, such as a suture hole to securely anchor the implantable device to the surrounding tissue. Housing91may in addition include a polyester ingrowth patch that facilitates attachment of the implantable device to the surrounding tissue following subcutaneous implantation.

Additionally, the implantable device optionally may incorporate anti-clogging agents, such enzyme eluting materials that specifically target the proteinaceous components of fluid from the peritoneal cavity, enzyme eluting materials that specifically target the proteinaceous and encrustation promoting components of urine, chemical eluting surfaces, coatings that prevent adhesion of proteinaceous compounds, and combinations thereof. Such agents, if provided, may be integrated within or coated upon the surfaces of the various components of the system.

Referring now toFIGS.4A to4D, further details of the gear pump and fluid path are described. InFIGS.4A-4D, like components are identified using the same reference numbers fromFIGS.3A and3B.FIG.4Ais an exploded view showing assembly of motor94with gear pump housing95and upper housing93, as well as the components of the fluid path within the implantable device. Upper housing93preferably comprises a high strength plastic or metal alloy material that can be molded or machined to include openings and channels to accommodate inlet nipple102, outlet nipple103, pressure sensors104a-104d, manifold105and screws106. Nipples102and103preferably are machined from a high strength biocompatible metal alloy, and outlet nipple103further includes channel107that accepts elastomeric duckbill valve108. Outlet nipple103further includes lateral recess109that accepts pressure sensor104a, which is arranged to measure pressure at the inlet end of the bladder catheter, corresponding to pressure in the patient's bladder (or peritoneal cavity).

Referring now also toFIGS.4B and4C, inlet nipple102is disposed within opening110, which forms a channel in upper housing93that includes opening111for pressure sensor104band opening112that couples to manifold105. Pressure sensor104bis arranged to measure the pressure at the outlet end of the peritoneal catheter, corresponding to pressure in the peritoneal cavity. Outlet nipple103, including duckbill valve107, is disposed within opening113of upper housing93so that lateral recess108is aligned with opening114to permit access to the electrical contacts of pressure sensor104a. Opening113forms channel115that includes opening116for pressure sensor104c, and opening117that couples to manifold105. Upper housing93preferably further includes opening118that forms a channel including opening119for accepting pressure sensor104d. Pressure sensor104dmeasures ambient pressure, and the output of this sensor is used to calculate differential pressures as described above. Upper housing further includes notch120for accepting connector26(seeFIG.4B) for retaining the peritoneal and bladder catheters coupled to inlet and outlet nipples102and103. Upper housing93further includes recess121to accept manifold105, and peg122, to which support member97(seeFIG.3B) is connected.

Manifold105preferably comprises a molded elastomeric component having two separate fluid channels (such channels designated88inFIG.3B) that couple inlet and outlet flow paths through upper housing93to the gear pump. The first channel includes inlet124and outlet125, while the second channel includes inlet126and outlet127. Inlet124couples to opening112(seeFIG.4C) of the peritoneal path and outlet127couples to opening117of the bladder path. Analyte sensor85(seeFIG.3B) may be located in communication with the peritoneal fluid path, or optionally located on catheter23. Manifold105is configured to improve manufacturability of the implantable device, by simplifying construction of upper housing93and obviating the need to either cast or machine components with complicated non-linear flow paths.

Motor94is coupled to gear pump housing95using mating threads130, such that splined shaft131of motor94passes through bearing132. The gear pump of the present invention comprises intermeshing gears133and134enclosed in gear pump housing95by O-ring seal135and plate136. The gear pump is self-priming. Plate136includes openings137and138that mate with outlet125and inlet126of manifold105, respectively. Splined shaft131of motor94extends into opening139of gear133to provide floating engagement with that gear.

Peritoneal and Bladder Catheters

Referring toFIGS.5A and5B, peritoneal catheter50may be Medionics International Inc.'s peritoneal dialysis Catheter, Model No. PSNA-100 or a catheter having similar structure and functionality. Peritoneal catheter50corresponds to peritoneal catheter23ofFIG.1, and may comprise tube51of medical-grade silicone including inlet (distal) end52having a plurality of through-wall holes53and outlet (proximal) end54. Holes53may be arranged circumferentially offset by about 90 degrees, as shown inFIG.5B. Peritoneal catheter50may also include a polyester cuff (not shown) in the region away from holes53, to promote adhesion of the catheter to the surrounding tissue, thereby anchoring it in place. Alternatively, inlet end52of peritoneal catheter50may have a spiral configuration, and an atraumatic tip, with holes53distributed over a length of the tubing to reduce the risk of clogging.

Inlet end52also may include a polyester cuff to promote adhesion of the catheter to an adjacent tissue wall, thereby ensuring that the inlet end of the catheter remains in position. Outlet end54also may include a connector for securing the outlet end of the peritoneal catheter to implantable device20. In one preferred embodiment, the distal end of the peritoneal catheter, up to the ingrowth cuff, may be configured to pass through a conventional 16 F peel-away sheath. In addition, the length of the peritoneal catheter may be selected to ensure that it lies along the bottom of the body cavity, and is sufficiently resistant to torsional motion so as not to become twisted or kinked during or after implantation.

With respect toFIG.6, an exemplary embodiment of bladder catheter60is described, corresponding to bladder catheter25ofFIG.1. Bladder catheter60preferably comprises tube61of medical-grade silicone having inlet (proximal) end62and outlet (distal) end63including spiral structure64, and polyester ingrowth cuff65. Bladder catheter60includes a single internal lumen that extends from inlet end62to a single outlet at the tip of spiral structure64, commonly referred to as a “pigtail” design. Inlet end62may include a connector for securing the inlet end of the bladder catheter to implantable device20, or may have a length that can be trimmed to fit a particular patient. In one embodiment, bladder catheter60may have length L3of about 45 cm, with cuff65placed length L4of about 5 to 6 cm from spiral structure64. Bladder catheter60may be loaded onto a stylet with spiral structure64straightened, and implanted using a minimally invasive technique in which outlet end63and spiral structure64are passed through the wall of a patient's bladder using the stylet. When the stylet is removed, spiral structure64returns to the coiled shape shown inFIG.6. Once outlet end63of bladder catheter60is disposed within the patient's bladder, the remainder of the catheter is implanted using a tunneling technique, such that inlet end62of the catheter may be coupled to implantable device20. Spiral structure64may reduce the risk that outlet end63accidentally will be pulled out of the bladder before the tissue surrounding the bladder heals sufficiently to incorporate ingrowth cuff65, thereby anchoring the bladder catheter in place.

In a preferred embodiment, bladder catheter60is configured to pass through a conventional peel-away sheath. Bladder catheter60preferably is sufficiently resistant to torsional motion so as not to become twisted or kinked during or after implantation. In a preferred embodiment, peritoneal catheter50and bladder catheter60preferably are different colors, have different exterior shapes (e.g., square and round) or have different connection characteristics so that they cannot be inadvertently interchanged during connection to implantable device20. Optionally, bladder catheter60may include an internal duckbill valve positioned midway between inlet62and outlet end63of the catheter to ensure that urine does not flow from the bladder into the peritoneal cavity if the bladder catheter is accidentally pulled free from the pump connector of implantable device20.

In an alternative embodiment, the peritoneal and bladder catheters devices may incorporate one or several anti-infective agents to inhibit the spread of infection between body cavities. Examples of anti-infective agents which may be utilized may include, e.g., bacteriostatic materials, bactericidal materials, one or more antibiotic dispensers, antibiotic eluting materials, and coatings that prevent bacterial adhesion, and combinations thereof. Additionally, implantable device20may include a UV lamp configured to irradiate fluid in the peritoneal and/or bladder catheters so as to kill any pathogens that may be present and thus inhibit the development of infection.

Alternatively, rather than comprising separate catheters, peritoneal and bladder catheters50,60may share a common wall as depicted inFIG.1, which may be convenient to facilitate insertion of a single dual-lumen tube. In addition, either or both of the peritoneal or bladder catheters may be reinforced along a portion of its length or along its entire length using ribbon or wire braiding or lengths of wire or ribbon embedded or integrated within or along the catheters. The braiding or wire may be fabricated from metals such as stainless steels, superelastic metals such as nitinol, or from a variety of suitable polymers. Such reinforcement may also be used for catheter46connected to optional reservoir45.

The Charging and Communication System

Referring toFIGS.7A,7B and8, charging and communication system150(corresponding to system30ofFIG.1) is described in greater detail. In one preferred embodiment, charging and communication system150comprises handpiece151and base31(seeFIG.1). Base31provides comprises a cradle for recharging handpiece151, and preferably contains a transformer and circuitry for converting conventional 120/220/240V power service to a suitable DC current to charge handpiece151when it is coupled to the base. Alternatively, handpiece151may include circuitry for charging the handpiece battery, and a detachable power cord. In this embodiment, handpiece151may be plugged into a wall socket for charging, and the power cord removed when the handpiece is used to recharge the implantable device.

As shown inFIG.8, handpiece151contains controller152, illustratively the processor of a micro-controller unit coupled to nonvolatile memory153(e.g., either EEPROM or flash memory), volatile memory154, radio transceiver155, inductive circuit156, battery157, indicator158and display159. Controller152, memories153and154, and radio transceiver155may be incorporated into a single microcontroller unit, such as the MPS430 family of microprocessors, available from Texas Instruments Incorporated, Dallas, Tex. Transceiver155is coupled to antenna160for sending and receiving information to implantable device20. Battery157is coupled to connector161that removably couples with a connector in base31to recharge the battery. Port162, such as a USB port or comparable wireless circuit, is coupled to controller152to permit information to be exchanged between handpiece151and the monitoring and control system. Inductive circuit156is coupled to coil163. Input device164, preferably a multi-function button, also is coupled to controller152to enable a patient to input a limited number of commands. Indicator158illustratively comprises a plurality of LEDs that illuminate to indicate the quality of charge coupling achieved between the handpiece and implantable device, and therefore assist in optimizing the positioning of handpiece151relative to the implantable device during recharging. In one preferred embodiment, indicator158is omitted, and instead a bar indicator provided on display159that indicates the quality-of-charging resulting from the coupling of coils163and84.

In a preferred embodiment, handpiece151includes a device identifier stored in nonvolatile memory153that corresponds to the device identifier stored in nonvolatile memory71of the implantable device, such that handpiece151will communicate only with its corresponding implantable device20. Optionally, a configurable handpiece for use in a physician's office may include the ability to interrogate an implantable device to request that device's unique device identifier, and then change the device identifier of the monitoring and control system40to that of the patient's implantable device, so as to mimic the patient's handpiece. In this way, a physician may adjust the configuration of the implantable device if the patient forgets to bring his handpiece151with him during a visit to the physician's office.

Controller152executes firmware stored in nonvolatile memory153that controls communications and charging of the implantable device. Controller152also is configured to transfer and store data, such as event logs, uploaded to handpiece151from the implantable device, for later retransmission to monitoring and control system40via port162, during physician office visits. Alternatively, handpiece151may be configured to recognize a designated wireless access point within the physician's office, and to wirelessly communicate with monitoring and control system40during office visits. As a further alternative, base31may include telephone circuitry for automatically dialing and uploading information stored on handpiece151to a physician's website via a secure connection, such as alarm information.

Controller152preferably includes a low-power mode of operation and includes an internal clock, such that the controller periodically awakens to communicate with the implantable device to log data or to perform charging functions. Controller152preferably is configured to awaken when placed in proximity to the implantable device to perform communications and charging functions, and to transmit commands input using input device164. Controller152further may include programming for evaluating information received from the implantable device, and generating an alarm message on display159. Controller152also may include firmware for transmitting commands input using input device164to the implantable device, and monitoring operation of the implantable device during execution of such commands, for example, during boost or jogging/shaking operation of the gear pump to clear a blockage. In addition, controller152controls and monitors various power operations of handpiece151, including operation of inductive circuit156during recharging of the implantable device, displaying the state of charge of battery74, and controlling charging and display of state of charge information for battery157.

Nonvolatile memory153preferably comprises flash memory or EEPROM, and stores the unique device identifier for its associated implantable device, firmware to be executed by controller152, configuration set point, and optionally, coding to be executed on transceiver155and/or inductive circuit156. Firmware and set point data stored on nonvolatile memory153may be updated using information supplied by control and monitoring system40via port162. Volatile memory154is coupled to and supports operation of controller152, and stores data and event log information uploaded from implantable device20.

In addition, in a preferred embodiment, nonvolatile memory153stores programming that enables the charging and communication system to perform some initial start-up functions without communicating with the monitor and control system. In particular, memory153may include routines that make it possible to test the implantable device during implantation using the charging and communication system alone in a “self-prime mode” of operation. In this case, a button may be provided that allows the physician to manually start the pump, and display159is used to provide feedback whether the pumping session was successful or not. Display159of the charging and communication system also may be used to display error messages designed to assist the physician in adjusting the position of the implantable device or peritoneal or bladder catheters. These functions preferably are disabled after the initial implantation of the implantable device.

Transceiver155preferably comprises a radio frequency transceiver, e.g., conforming to the Bluetooth or IEEE 802.11 wireless standards, and is configured for bi-directional communications via antenna160with transceiver circuit76disposed in the implantable device. Transceiver155also may include a low power mode of operation, such that it periodically awakens to listen for incoming messages and responds only to those messages including the unique device identifier assigned to its associated implantable device. Transceiver155preferably employs an encryption routine to ensure that messages sent to, or received from, the implantable device cannot be intercepted or forged.

Inductive circuit156is coupled to coil163, and is configured to inductively couple with coil84of the implantable device to recharge battery74of the implantable device. In one embodiment, inductive circuit156is coupled to indicator158, preferably a plurality of LEDs that light to indicate the extent of magnetic coupling between coils163and84(and thus quality of charging), thereby assisting in positioning handpiece151relative to the implantable device. In one preferred embodiment, inductive coils84and163are capable of establishing good coupling through a gap of 35 mm, when operating at a frequency of 315 kHz or less. In an embodiment in which implantable device includes optional infrared LED83, charging and communication system30may include an optional infrared sensor (not shown) which detects that infrared light emitted by LED83and further assists in positioning handpiece151to optimize magnetic coupling between coils163and84, thereby improving the energy transmission to the implantable device.

Controller152also may be configured to periodically communicate with the implantable device to retrieve temperature data generated by temperature sensor78and stored in memory72during inductive charging of battery74. Controller152may include firmware to analyze the battery temperature, and to adjust the charging power supplied to inductive circuit163to maintain the temperature of the implantable device below a predetermined threshold, e.g., less than 2 degrees C. above body temperature. That threshold may be set to reduce thermal expansion of the battery and surrounding electronic and mechanical components, for example, to reduce thermal expansion of motor and gear pump components and to reduce the thermal strain applied to the seal between lower portion92of housing and upper housing93. In a preferred embodiment, power supplied to inductive coil163is cycled between high power (e.g., 120 mA) and low power (e.g., 40 mA) charging intervals responsive to the measured temperature within the implantable device.

As discussed above with respect to inductive circuit75of the implantable device, inductive circuit156optionally may be configured to transfer additional power to motor73of the implantable device, via inductive circuit75and battery74, in a “boost” mode or jogging mode to unblock the gear pump. In particular, if an alarm is transmitted to smartphone50or controller152that motor73is stalled, e.g., due to a block created by viscous fluid, the patient may be given the option of using smartphone50or input device164to apply an overvoltage to motor73from battery74and/or inductive circuit75for a predetermined time period to free the blockage. Alternatively, activating input device164may cause controller152to command processor70to execute a routine to jog or shake the gear pump by rapidly operating motor74in reverse and forward directions to disrupt the blockage. Because such modes of operation may employ higher energy consumption than expected during normal operation, inductive circuits156and75may be configured to supply the additional energy for such motor operation directly from the energy stored in battery157, instead of depleting battery74of the implantable device.

Battery157preferably comprises a lithium ion or lithium polymer battery capable of long lasting operation, e.g., up to three years. Battery157has sufficient capacity to supply power to handpiece151to operate controller152, transceiver155, inductive circuit156and the associated electronics while disconnected from base31and during charging of the implantable device. In a preferred embodiment, battery157has sufficient capacity to fully recharge battery74of the implantable device from a depleted state in a period of about 2-4 hours. Battery157also should be capable of recharging within about 2-4 hours. It is expected that for daily operation moving 700 ml of fluid, battery157and inductive circuit156should be able to transfer sufficient charge to battery74via inductive circuit75to recharge the battery within about 30 minutes. Battery capacity preferably is supervised by controller152using a charge accumulator algorithm.

Referring again toFIGS.7A and7B, handpiece151preferably includes housing165having multi-function button166(corresponding to input device164ofFIG.8) and display167(corresponding to display159ofFIG.8). A plurality of LEDs168is disposed beneath a translucent portion of handpiece151, and corresponds to indicator158ofFIG.8. Port169enables the handpiece to be coupled to monitoring and control system40(and corresponds to port162ofFIG.8), while connector170(corresponding to connector161inFIG.8) permits the handpiece to be coupled to base31to recharge battery157. Multi-function button166provides the patient the ability to input a limited number of commands to the implantable device. Display167, preferably an OLED or LCD display, provides visible confirmation that a desired command input using multifunction button166has been received. Display167also may display the status and state of charge of battery74of the implantable device, the status and state of charge of battery157of handpiece151, signal strength of wireless communications, quality-of-charging, error and maintenance messages. Inductive coil portion171of housing165houses inductive coil163.

LEDs168are visible through the material of housing165when lit, and preferably are arranged in three rows of two LEDs each. During charging, the LEDs light up to display the degree of magnetic coupling between inductive coils163and84, e.g., as determined by energy loss from inductive circuit156, and may be used by the patient to accurately position handpiece151relative to the implantable device. Thus, for example, a low degree of coupling may correspond to lighting of only two LEDs, an intermediate degree of coupling with lighting of four LEDs, and a preferred degree of coupling being reflected by lighting of all six LEDs. Using this information, the patient may adjust the position of handpiece151over the area where implantable device is located to obtain a preferred position for the handpiece, resulting in the shortest recharging time. In one preferred embodiment, LEDs168are replaced with an analog bar display on display167, which indicates the quality of charge coupling.

Monitoring and Control System

Turning toFIG.9, the software implementing monitoring and control system40ofFIG.1will now be described. Software180comprises a number of functional blocks, schematically depicted inFIG.9, including main block184, event logging block182, data download block183, configuration setup block184, user interface block185, alarm detection block186including health monitor block191and analyte monitoring block192, sensor calibration block187, firmware upgrade block188, device identifier block189and status information block190. In one embodiment, the software is coded in C++ and employs an object oriented format, although other software languages and environments could be used. In one embodiment, the software is configured to run on top of a Microsoft Windows® (a registered trademark of Microsoft Corporation, Redmond, Wash.) or Unix-based operating system, such as are conventionally employed on desktop and laptop computers, although other operating systems could be employed.

The computer running monitoring and control system software180preferably includes a data port, e.g., USB port or comparable wireless connection that permits handpiece151of the charging and communication system to be coupled via port169. Alternatively, as discussed above, the computer may include a wireless card, e.g., conforming to the IEEE 802.11 standard, thereby enabling handpiece151to communicate wirelessly with the computer running software180. As a further alternative, the charging and communication system may include telephony circuitry that automatically dials and uploads data, such as alarm data, from handpiece151to a secure website accessible by the patient's physician.

Main block184preferably consists of a main software routine that executes on the physician's computer, tablet or smartphone, and controls overall operation of the other functional blocks. Main block184enables the physician to download event data and alarm information stored on handpiece151to their computer, tablet or smartphone, and also permits control and monitoring software180to directly control operation of the implantable device when coupled to handpiece151. Main block also enables the physician to upload firmware updates and configuration data to the implantable device.

Event Log block182is a record of operational data downloaded from the implantable device via the charging and communication system, and may include, for example, pump start and stop times, motor position, sensor data for the peritoneal cavity and bladder pressures, patient temperature, respiratory rate or fluid temperature, pump outlet pressure, humidity, pump temperature, battery current, battery voltage, battery status, and the like. The event log also may include the occurrence of events, such as pump blockage, operation in boost or jog modes, alarms or other abnormal conditions.

Data Download block183is a routine that handles communication with handpiece151to download data from volatile memory154after the handpiece is coupled to the computer running monitoring and control software180. Data Download block183may initiate, either automatically or at the instigation of the physician via user interface block185, downloading of data stored in the event log.

Configuration Setup block184is a routine that configures the parameters stored within nonvolatile memory71that control operation of the implantable device. The interval timing parameters may determine, e.g., how long the processor remains in sleep mode prior to being awakened to listen for radio communications or to control pump operation. The interval timing parameters may control, for example, the duration of pump operation to move fluid from the peritoneal cavity to the bladder, the pump speeds to be used during specific phases of the DSR therapy, and the interval between periodic tick movements that inhibit blockage of the implantable device and peritoneal and bladder catheters. Interval timing settings transmitted to the implantable device from monitoring and control software180also may determine when and how often event data is written to nonvolatile memory71, and to configure timing parameters used by the firmware executed by processor152of handpiece151of the charging and communication system. Block184also may be used by the physician to configure parameters stored within nonvolatile memory71relating to limit values on operation of processor70and motor73, and to set target and threshold values. These values may include the sodium concentration detected in the peritoneal catheter at which fluid transfer to the bladder should be initiated, maximum DSR solution dwell time, minimum and maximum pressures at the peritoneal and bladder catheters, the maximum temperature differential during charging, times when the pump may and may not operate, etc. The limit values set by block184also configure parameters that control operation of processor152of handpiece151.

Block184also may configure parameters store within nonvolatile memory71of the implantable device relating to control of operation of processor70and motor73. These values may include target volumes of fluid to transport, volume of fluid to be transported per pumping session, motor speed and duration per pumping session. Block184also may specify the parameters of operation of motor73during boost mode of operation and shake/jog modes of operation. Such parameters may include motor speed and voltage, duration/number of revolutions of the motor shaft when alternating between forward and reverse directions, etc.

User interface block185handles display of information retrieved from the monitoring and control system and implantable device via data download block183, and presents that information in an intuitive, easily understood format for physician review. As described below with respect toFIG.10, such information may include status of the implantable device, status of the charging and control system, measured pressures, volume of fluid transported per pumping session or per day, etc. User interface block185also generates user interface screens that permit the physician to input information to configure the interval timing, limit and pump operation parameters discussed above with respect to block184.

Alarm detection block186may include a routine for evaluating the data retrieved from the implantable device or charging and communication system, and flagging abnormal conditions for the physician's attention, and determining whether a specific alarm condition should be reported to smartphone50to prompt immediate patient action. Alarm detection block186also may include health monitor block191, which is configured to alert the patient or physician to any changes in the patient's health that may warrant changing the volume, time, and/or frequency with which the DSR therapy is conducted.

Sensor calibration block187may include routines for testing or measuring drift, of sensors70,78-81and85employed in the implantable device, e.g., due to aging or change in humidity. Block187may then compute offset values for correcting measured data from the sensors, and transmit that information to the implantable device for storage in nonvolatile memory71. For example, pressure sensors104a-104dmay experience drift due to aging or temperature changes. Block187accordingly may compute offset values that are then transmitted and stored in the implantable device to account for such drift.

Firmware upgrade block188may comprise a routine for checking the version numbers of the processor or motor controller firmware installed on the implantable device and/or processor firmware on charging and communication system, and identify whether upgraded firmware exists. If so, the routine may notify the physician and permit the physician to download revised firmware to the implantable device for storage in nonvolatile memory71or to download revised firmware to the charging and communication system for storage in nonvolatile memory153.

Device identifier block189consists of a unique identifier for the implantable device that is stored in nonvolatile memory71and a routine for reading that data when the monitoring and control system is coupled to the implantable device via the charging and communication system. As described above, the device identifier is used by the implantable device to confirm that wireless communications received from a charging and communication system are intended for that specific implantable device. Likewise, this information is employed by handpiece151of the charging and communication system in determining whether a received message was generated by the implantable device associated with that handpiece. Finally, the device identifier information is employed by monitoring and control software180to confirm that the handpiece and implantable device constitute a matched set.

Status information block190comprises a routine for interrogating implantable device, when connected via handpiece151, to retrieve current status date from the implantable device, and/or handpiece151. Such information may include, for example, battery status, the date and time on the internal clocks of the implantable device and handpiece, version control information for the firmware and hardware currently in use, and sensor data. Status information block190also may make some or all of the preceding information available to smartphone50for display to the patient.

Referring now toFIG.10, an exemplary screen shot generated by user interface block185of software180is described for an implantable system used in accordance with the methods of the present invention for conducting DSR therapy.FIG.10shows main screen200, which may be displayed on monitoring and control system40, and includes a status area that displays status information retrieved from the implantable device and the charging and communication system by the routine corresponding to block190ofFIG.9. More particularly, the status area includes status area201for the charging and communication system (referred to as the “Smart Charger) and status area202for the implantable device (referred to as the “ALFA Pump”). Each status area includes an icon showing whether the respective system is operating properly, indicated by a checkmark, the device identifier for that system, and whether the system is connected or active. If a parameter is evaluated by the alarm detection block186to be out of specification, the icon may instead include a warning symbol. Menu bar203identifies the various screens that the physician can move between by highlighting the respective menu item. Workspace area204is provided below the status area, and includes a display that changes depending upon the menu item selected. Below workspace area204, navigation panel205is displayed, which includes the version number of software180and a radio button that enables the displays in workspace area204to be refreshed.

InFIG.10, the menu item “Information” with submenu item “Implant” is highlighted in menu bar203. For this menu item selection, workspace area204illustratively shows, for the implantable device, battery status window204a, measured pressures window204band firmware version control window204c. Battery status window204aincludes an icon representing the charge remaining in battery74, and may be depicted as full, three-quarters, one-half, one-quarter full or show an alarm that the battery is nearly depleted. The time component of window204aindicates the current time as received from the implantable device, where the date is expressed in DD/MM/YYYY format and time is expressed in HR/MIN/SEC format based on a 24-hour clock. Measured pressures window204bdisplays the bladder pressure, peritoneal pressure and ambient pressures in mBar measured by sensors104a,104band104drespectively (seeFIG.4A). Version control window204cindicates the firmware version for processor70, for the motor controller, and the hardware version of the implantable device. Patient parameters window204ddisplays the patient's temperature, respiratory rate, and intra-abdominal pressure. Note that if implantable device included other types of sensors, e.g., sensors that measure the levels of fluid in the body, then the parameters measured by such sensors could also be displayed in window204d.

Alarm condition window204edisplays any changes in parameters that may indicate a change in the patient's health, such as the possible development of heart failure decompensation or an improvement or worsening of the patient's health (Block186inFIG.9). For example, as illustrated, alarm condition window204emay alert the patient and/or physician that the patient's intra-abdominal pressure is abnormally high, so that the patient and physician then may follow up to rectify that situation. In some embodiments, based on information displayed in windows204b,204d, and/or204e, the physician may adjust the operating parameters of the pump.

Arrangements for Handling DSR Solution

Referring now toFIG.11, a first catheter arrangement for instilling fluid into a patient's peritoneal cavity at the initiation of a DSR therapy session is described. Device20is implanted subcutaneously, preferably outside of the patient's peritoneal cavity as defined by peritoneal membrane P. Implantable device20is placed beneath skin S so that the device may readily be charged by, and communicate with, charging and communication system30. Subcutaneous port210includes a self-healing membrane211and is implanted in the patient's upper abdomen, and is coupled to peritoneal catheter23by tee connector212and instillation line213. Tee connector212is coupled to the inlet port of implantable device20by tubing214. The outlet port of implantable device20is coupled to bladder catheter25, thereby enabling implantable device20to transfer fluid from the peritoneal cavity to the patient's bladder at the completion of the DSR therapy session.

In accordance with one aspect of the invention, tee connector212optionally may include a valve, that selectively permits fluid to flow from subcutaneous port210, through instillation line213and into peritoneal cavity P via peritoneal catheter23, but prevents instilled DSR solution from passing to the inlet port of implantable device20. Sterile DSR solution disposed in bag220, is coupled via tubing221to non-coring needle222, which may be inserted through patient's skin S and self-healing membrane211to place the contents of bag220in fluid communication with the interior of subcutaneous port210. In this manner, DSR solution from bag220, typically 0.5 up to 2 liters, will flow through tubing221and needle222into subcutaneous port210, and then into the peritoneal cavity via instillation line213, tee junction212and peritoneal catheter23. The DSR solution thus instilled with initiate the DSR therapy session while simultaneously flushing peritoneal catheter23of debris that could potentially block the catheter when the DSR and ultrafiltrate subsequently is withdrawn.

After instillation of the DSR solution from bag220is completed, needle221is withdrawn. Later, upon completion of the dwell period, for example, as may be determined by expiration of a specified time interval, detected analyte concentration, or rate of change of intraabdominal pressure, implantable device20is actuated to suck fluid from the peritoneal cavity via the peritoneal catheter, tee junction212and tubing214to implantable device20. No fluid is drawn through instillation line213as the valve in tee-connector212isolates the instillation line from pump suction. Fluid drawn into peritoneal catheter23is pumped by implantable device20through bladder catheter25and into the patient's bladder.

Alternatively, tee connector212may be employed without a valve. In this case, some DSR solution may be lost as directly flowing into the bladder through implantable device20, and not into the peritoneum. However, it is expected that the gears of the implantable device20will impede fluid loss through the pump, and accordingly the loss would be small. Moreover, the expected DSR loss through the pump during instillation could be empirically determined, and thus taken into consideration for dosing of the DSR solution for a given DSR therapy session. For example, if was empirically known that 100 ml is lost during infusion of 1000 ml into the abdomen, an 1100 ml total dose may be proscribed for infusion. On the other hand, during operation of implantable device20to move fluid from the peritoneal cavity to the bladder, suction induced by the pump would not pose a problem for instillation line213or subcutaneous port210because the subcutaneous port will remain closed via operation of self-healing membrane211.

Referring now toFIGS.12,13A and13B, an alternative arrangement for instilling DSR fluid into a patient's peritoneum is described. As for the arrangement ofFIG.11, device20is implanted subcutaneously, preferably outside of the patient's peritoneal cavity as defined by peritoneal membrane P. Implantable device20is placed beneath skin S so that the device may readily be charged by, and communicate with, charging and communication system30. Subcutaneous port230includes a self-healing membrane231and is implanted in the patient's upper abdomen, and is coupled to peritoneal catheter23by Y-connector232and instillation line233. Y-connector232is coupled to the inlet port of implantable device20by tubing234. The outlet port of implantable device20is coupled to bladder catheter25, thereby enabling implantable device20to transfer fluid from the peritoneal cavity to the patient's bladder at the completion of the DSR therapy session.

Y-connector212is configured to permit fluid to flow from subcutaneous port230, through instillation line231and into peritoneal cavity P via peritoneal catheter23, but reduces the amount of instilled DSR solution that can pass to the inlet port of implantable device20. As for the preceding arrangement, sterile DSR solution disposed in bag220, is coupled via tubing221to non-coring needle222, which may be inserted through patient's skin S and self-healing membrane231to place the contents of bag220in fluid communication with the interior of subcutaneous port230. Accordingly, DSR solution from bag220, typically 0.5 up to 2 liters, will flow through tubing221and needle222into subcutaneous port230, and then into the peritoneal cavity via instillation line233, Y-connector232and peritoneal catheter23. DSR solution instilled in this matter at the start of the DSR therapy session simultaneously will flush peritoneal catheter23of debris that could potentially block the catheter when the DSR and ultrafiltrate subsequently is withdrawn.

After instillation of the DSR solution from bag220is completed, needle221is withdrawn. Later, upon completion of the dwell period, as described above, implantable device20is actuated to suck fluid from the peritoneal cavity via peritoneal catheter23, Y-connector232and tubing234to implantable device20. The configuration of Y-connector232preferably is designed so that during delivery of DSR solution through instillation line233, hydraulic forces induced by the flow through the Y-connector will reduce lost flow to the bladder through implantable device20. In particular, when pressure is applied to instillation line233coupled to the Y-connector, based on fluid dynamics principles, the vast majority of flow and pressure will exit the lower end of Y-connector232towards peritoneal catheter23, which is thus flushed. Relatively little is expected to reach “backwards” into the other upper end of the Y-connector and thus slip-flow through the pump is reduced. Moreover, as for the embodiment of the tee connector without a valve, it is expected that the gears of the implantable device20will impede fluid loss through the pump, thus further reducing loss of DSR loss through the pump during instillation. In addition, such lost amounts could be empirically determined, such that a slightly larger dose of DSR solution may be proscribed for infusion. Fluid drawn into peritoneal catheter23is pumped by implantable device20through bladder catheter25and into the patient's bladder.

Referring now toFIGS.13A and13B, another aspect of the Y-connector is described. As depicted inFIG.13A, the Y-connector may be supplied as a separate component of the catheter arrangement, which is assembled by the implanting surgeon or physician when implantable device20is first implanted in the patient. As depicted inFIG.13A, each end of Y-connector232should have circumference protuberances236,237and238which serve to retain line233, tubing234and catheter23installed onto the respective ends of the Y-connector. As shown inFIG.13B, the physician or surgeon also may apply suture239through line233, tubing234and catheter23during the implantation procedure to tightly close and bind those components to Y-connector232, thus ensuring that the components are not pulled free from the Y-connector during normal expected use. Alternatively, a plastic zip tie or similar device may be used in lieu of sutures to join the various tubing components to the Y-connector. As a still further alternative, the connector may include snap rings or other suitable structure to fasten the tubes to the Y-connector to secure the tubing from separating.

In accordance with a further aspect of the invention, the implantable device could be programmed to include a flush feature, which could be implemented by a command issued from smartphone50, charging and communication system30or monitoring and control system40to avoid exposing implantable device20to excessive high pressures during instillation for the DSR solution and flushing of peritoneal catheter23. In particular, issuing the command to implantable device20could activate the built-in pressure sensors monitor the applied pressure and report to a connected charging and control system30or smartphone50. If detected pressure is zero or low, a signal indicating acceptable status could be sent to the connected device. However, once a threshold pressure is attained that would be dangerous to the pump mechanics, or the patient, a warning signal could be provided to the connected device. If pressure continued to rise further, an alarm condition could be generated, indicating to the patient that the flushing pressure needs to be immediately reduced.

Referring now toFIG.14, methods of using the implantable system ofFIG.1to conduct a DSR therapy session are described. Method250includes introducing no or low sodium DSR solution into the peritoneal cavity, for example, using an arrangement as described above with respect toFIG.11or12. A sufficient amount of DSR solution, generally 0.5 up to about 2 liters, is introduced into the peritoneal cavity of the patient and allowed to a desired threshold is attained, such as expiration of a specified dwell time, detection of a target analyte concentration, or intraabdominal pressure. As described in the above-incorporated patent and application, the goal of the DSR therapy session is to draw excess fluid and/or sodium from the patient's body tissues into the peritoneal cavity, from which it is removed to the bladder via implantable device20.

In step254, a number of physiologic parameters may be monitored as indicative of the status of the DSR therapy session, including the analyte concentration in the patient's peritoneal cavity, the intraabdominal pressure and bladder pressure. At step256, the rate of change with time of the measured analyte concentration in the DSR solution and fluid accumulated in the peritoneal cavity may be compared to a target value. For example, if the rate of change of the sodium concentration within the fluid in the peritoneal cavity is initially high but begins to decrease over time, that observed value may indicate further extending the dwell time will not result in significant additional fluid or sodium migration to the peritoneum, and thus the current session should be ended. That determination then may be used to initiate pumping of fluid from the peritoneal cavity to the patient's bladder.

The target value may be downloaded to implantable device by the physician using software monitoring and control system40via external charging and communication system30prior to initiating the DSR therapy session. Alternatively, the target value may be static, i.e., programmed one time, or may be revised prior to each DSR therapy session based on prior results for that patient and titrated to provide a targeted blood sodium serum level by completion of the DSR therapy session. Alternatively, the target value may consist of another value of interest for a particular patient, such as a target quantity of sodium to be removed during the DSR therapy session, or a target value of an infusate concentration at which pumping is to begin and/or cease.

If at step256the monitored value is less than the target value (“No” branch at step256), the processor of implantable device20then may evaluate at step258whether the current dwell time for the DSR solution exceeds the maximum dwell time for that DSR therapy session. The maximum dwell time may be a static value that is programmed once, or a value that is set prior to each DSR therapy session as may be determined by the physician. If the current dwell time is less than the maximum value (“No” branch at step258), the processor may internally set another time interval, e.g., 5 or 10 minutes, after which it will continue to monitor the specified parameter at step254and evaluate whether the target has been attained at step256. If however, the maximum dwell time has been exceeded at step258, then the processor will activate the pump of implantable device20to begin transferring sodium-rich DSR solution and ultrafiltrate from the peritoneal cavity to the patient's bladder, at step260(“Yes” branch at step258). Referring back to the decision box at step256, if the monitored value equals or exceeds the target value (the “Yes” branch at step256), the processor also will activate the pump of implantable device20at step260.

Once the pump of implantable device20is activated, it will transfer fluid from the peritoneal cavity to the bladder via bladder catheter25. To ensure that the pump motor does not overheat from continuous operation, the pump may run for a predetermined specified interval, e.g., 5 or 10 minutes, then rest for a brief interval, e.g., 2-5 minutes, and then resume operation. Alternatively, the pump may run at different speeds for different intervals of the pumping period. If the pump is actuated periodically in this manner to complete removal of the DSR solution and accumulated ultrafiltrate from the peritoneal cavity, for example, as determined by the pressure in the peritoneal cavity falling below a target value, the processor may no longer require that the detected physiologic parameter(s) exceed the target level for that particular DSR therapy session. Accordingly, once the threshold is satisfied or the dwell time exceeded for a particular DSR therapy session, the pump will be actuated intermittently until drainage of the peritoneal cavity is determined to be complete.

Apart from intermittent operation to permit brief periods for the pump to rest, or operation at different flow rates, as described above, the processor also monitors the patient's bladder pressure to ensure that transfer of fluid to the bladder is interrupted when the bladder is deemed to be full. Fullness may be determined by the physician receiving oral feedback of discomfort from the patient during initial set-up and programming of implantable device20. Accordingly, at step262, bladder pressure is monitored, particularly at times when fluid is being transferred to the bladder. If the bladder pressure is lower than the level associated with bladder fullness, as initially programmed (“No” branch at step262), the processor next evaluates whether the pressure in the peritoneal cavity is greater than a predetermined target pressure at step264. The target pressure at step264is a pressure determined to correspond to fluid accumulation in the patient's peritoneal cavity, which value may set during initial implantation and then periodically updated by the physician using monitoring and control system40during the course of multiple DSR therapy sessions. If at step264that peritoneal pressure indicates that peritoneal cavity still contains fluid to be transferred to the bladder, the pump of implantable device20may remain active, change speeds, or if at rest, resume operation to transfer fluid to the bladder (“Yes” branch at step264). If the peritoneal cavity pressure is determined at step264to be less than target pressure (“No” branch at step264), the processor will deactivate the pump and store a record reflecting completion of that DSR therapy session in the non-volatile memory for eventual transmission to event log182(seeFIG.9).

Referring again to step262, if the processor of implantable device20detects that the pressure of fluid in the patient's bladder exceeds the target value (“Yes” branch at step262), the processor will cease pumping and movement of fluid to the patient's bladder. The processor then will set a timer, at step266, during which implantable device20waits until the patient voids his bladder. Once the patient voids his bladder and the bladder pressure drops below the target level, the processor again activates the pump to transfer remaining fluid in the peritoneal cavity to the bladder.

As described above, actuation of the pump transfers sodium-laden DSR solution and ultrafiltrate from the peritoneal cavity to the bladder, thereby reducing the level of sodium in the body and causing elimination of excess fluid by i) enhancing normal kidney function through urination and ii) removal to the bladder of osmotic ultrafiltrate that accumulates in the peritoneal cavity. It is expected that by configuring to activate the pump responsive to a monitored parameter of the fluid in the peritoneal cavity, better control of serum sodium concentration may be maintained than could be achieved by basing the action of the DSR solution on dwell time alone.

Energy may be wirelessly transferred to the implantable device, and data received from the device, using charging and communication system30described above with reference toFIG.1. For example, the implantable device may record parameters reflective of the health of the patient and the operation of the device, which parameters may be communicated to the charging and communication system or patient's smartphone. The data, e.g., parameters recorded by the implantable device, also may be provided to monitoring and control software40, via the charging and communication system. Based on those parameters, the health of the patient may be assessed using the software, and the physician may remotely communicate any modifications to the target analyte concentration, target pressures, flow rates, volume, dwell time, or frequency with which the implantable device is activated to transfer DSR solution and ultrafiltrate containing the extracted sodium to the bladder. Such communication may be performed via the charging and communication system.

While various illustrative embodiments of the invention are described above, it will be apparent to one skilled in the art that various changes and modifications may be made therein without departing from the invention. For example, the implantable device may be ordered differently and may include additional or fewer components of various sizes and composition. The appended claims are intended to cover all such changes and modifications that fall within the true spirit and scope of the invention.