JP7048504B2 - Devices and methods for screening patients for bladder control via pudendal nerve stimulation - Google Patents

Description

Cross-reference to related applications This application claims the benefit of priority under US Provisional Application No. 62 / 294,613 (Agent Document No. 42197-739.101) filed on February 12, 2016. This application is also a partial continuation of US Patent Application No. 15 / 153,314 filed May 12, 2016; the entire content of these applications is incorporated by reference in its entirety. Will be done.

This application is also in connection with US Patent Application No. 15 / 410,692, filed January 19, 2017, which is incorporated herein by reference for all purposes. ..
Background of the invention The field of invention. The present invention relates to medical devices and methods. More specifically, the present invention relates to a system and method for screening paralyzed and incontinent patients and determining whether they can benefit from pudendal nerve stimulation to control urethral function.

Many disorders can result in a loss of the patient's ability to spontaneously control bladder function. Most commonly, patients with spinal cord injuries may lose not only the ability to control urination spontaneously, but also the ability to sense when the bladder fills. Such patients need to rely on chronic use of urinary (Foley) catheters, which are usually placed through the urethra and have a distal tip residing in the bladder. Such Foley catheters present a certain risk of infection, which is exacerbated by the frequent need to replace a clogged catheter with a new one. In addition, Foley catheters typically drain into a bag, which must be transported when the patient leaves home or treatment facility. The need to transport the drain bag is a significant burden for many patients.

To overcome these problems, at least in part, a very promising new system has been proposed that allows patients and their caregivers to selectively stimulate the pudendal nerves and excrete from the bladder. Allows you to control. Such a system can eliminate the need for Foley catheters and is described, for example, in US Patent Publication No. 2014/0249595, which is incorporated herein by reference in its entirety.

Although significant progress, such pudendal nerve stimulation systems require surgical implantation of stimulating electrodes in the vicinity of the pudendal nerve, and the system is not always successful, but for removal. , A second surgery may be required.

For these reasons, it would be desirable to provide improved systems and methods for controlling urination via stimulation of the pudendal nerve. In particular, it is desirable to provide equipment and methods that allow patient testing to determine if such pudendal nerve stimulation is effective and the likelihood that implant surgery can be guaranteed. There will be.

2. 2. Explanation of background technology. U.S. Patent Application Publication No. 2014/0249595 is described above. See also U.S. Patent Application Publication Nos. 2014/0058284, 2014/0058588, and 2014/0309550.

U.S. Patent Application Publication No. 2014/0249595 U.S. Patent Application Publication No. 2014/0058284 U.S. Patent Application Publication No. 2014/0058588 U.S. Patent Application Publication No. 2014/0309550

Abstract of the Invention An embodiment of the present invention is intended for implantation of a neurostimulator intended to control urination in a patient who is unable or otherwise impaired in urination. Prior to that, a device and a method for testing a patient are provided. Such patients can include paralyzed patients or any patient with urethral dysfunction that interferes with their ability to spontaneously control urination. A particular embodiment of the invention is to test a patient and determine if he or she will benefit from such an implanted neurostimulation therapy that allows the patient to control bladder excretion. Devices, systems, and methods. Nerve stimulation treatments intended to control urination typically require implantation of electrodes to stimulate the pudendal nerve and cable leads or wiring between the controller and the controller and electrodes. .. By selectively stimulating the pudendal nerve with high and low frequency currents, the bladder contracts, the urethral sphincter muscles are opened, and urination can be controlled without the need for a Foley catheter to reside in the patient's urethra. can do. However, before implanting such a device, it may be desirable to determine if the patient is likely to benefit from pudendal nerve stimulation. In various embodiments of the invention, the stimulation protocol fills the bladder and applies a stimulation current to the pudendal nerve, one or more physiologically involved in the urinary process, such as relaxation of the urethral sphincter and contraction of the bladder. Allows to be mimicked using a temporarily introduced urethral catheter that can be used both for testing the ability to control bladder excretion by inducing or producing action. .. Embodiments of the invention specifically, i) selected systems and / or protocols for controlling and / or optimizing urination, via electrical stimulation of the pudendal nerve, control urination with respect to a given patient. To determine if it is effective, ii) adjust or otherwise adjust the properties of one or more of the electrical stimuli and control the urethral function and / or control produced by pudendal nerve treatment in a particular patient. Useful for optimizing or otherwise improving. Such properties may include the frequency, current, or voltage of the electrical stimulus used and one or more of the waveforms of such stimuli.

In the first aspect, the invention provides a method for screening a patient and determining the likelihood that the patient will benefit from pudendal nerve stimulation therapy. A catheter is temporarily introduced through the patient's urethra and the distal end of the catheter enters the patient's bladder. The catheter is used to fill the bladder with a fluid such as water or saline, and at least one electrode on the catheter conducts an electric current, typically in or near the patient's urethral sphincter, in the patient's pubic area. It is located within the urethra at a location selected for delivery to the nerve. A low frequency current is delivered to the pudendal nerve using electrodes to contract the patient's bladder, and a high frequency current is delivered to the pudendal nerve to open the patient's urethral sphincter. The patient is able to deliver low and high frequency currents to successfully contract the bladder and open the urethral sphincter, and in response to the delivered current, the fluid introduced into the bladder. Is considered likely to benefit from pudendal nerve treatment if it allows it to be excreted. In one aspect of the method, the catheter may further include a first pressure sensor that allows the pressure in the bladder to be measured. Usually, the pressure sensor is at or near the distal end of the catheter and may lie inside the bladder. A first pressure sensor, located at or near the distal end of the catheter, is as the bladder is filled and filled to target pressure prior to the user delivering current and testing bladder excretion. , Allows monitoring of bladder pressure.

Embodiments of the present invention contemplate various current delivery schemes that can be used to assess the effectiveness of pudendal nerve stimulation in controlling urethral function. Typically, high and low frequency currents can be delivered in parallel, but non-parallel delivery is also contemplated. Delivery of current may be initiated at the same time. However, in one or more embodiments, one may be started before the other and / or one may be stopped before the other. For example, according to one embodiment of the current delivery scheme, a high frequency current can first be delivered to relax the urethral sphincter. A low frequency current is then initiated and maintained for a selective period to contract and excrete the bladder. The low frequency current is then stopped after a selected period, while the high frequency leaves the urethral sphincter muscle open, allowing urine to continue to flow due to any residual contraction of the bladder. Continued to be. Finally, the high frequency current is also stopped and the urethral sphincter is closed.

One, two, or all three of bladder pressure, sphincter pressure, and observed urinary flow (qualitative and quantitative) are used to assess possible therapeutic efficacy. You may. In certain embodiments, one, two, or all three of these parameters may also be used to determine either or both of the optimal high frequency and optimal low frequency currents. May be used to generate selection and / or maximum urethral flow velocity in subsequent treatment. For example, in one particular embodiment, one or both of the bladder pressure and urethral flow velocity are used by a therapeutic low and / or high frequency current for a particular patient, ie, subsequently implanted, therapeutic device. Can be used to preselect the low or high frequencies to obtain. In another embodiment, one or both of the urethral flow velocity and the urethral sphincter pressure can be used for such preselection. Thus, the selection and / or configuration of implanted therapeutic devices is optimized to provide maximum urethral function to each patient before they have any implanted devices such as electrodes, wire controllers, etc. Can be done.

In another embodiment of the invention, at least two electrodes are positioned on the catheter and can deliver an electric current to the pudendal nerve. The first electrode may be configured to deliver a low frequency current and the second electrode may be configured to deliver a high frequency current.

In yet another embodiment of the invention, the contractile pressure exerted by the patient's urethral sphincter can be measured. Typically, the contraction pressure is measured by a second pressure sensor on the catheter, and the second pressure sensor and optionally the first and optionally the second stimulus electrode, usually the electrode and the pressure sensor, respectively, have the catheter. When the distal end is in the bladder and in the urethra, it is positioned on the catheter body so that it is close to or in the urethral sphincter that surrounds the urethra. Further optionally, the catheter, such as a balloon on a Foley catheter, allows the catheter to be positioned by retracting the catheter until the balloon or other anchor is seated against or within the bladder neck. A balloon or other anchor structure may be included in the vicinity of its distal end. By selectively positioning the electrodes and the second pressure sensor, these elements are properly positioned with respect to the urethral sphincter when the catheter is in place.

In the second aspect, the present invention screens the patient prior to the pudendal nerve stimulation treatment, i.e., the patient for the effectiveness of the pudendal nerve stimulation treatment prior to implantation of the therapeutic pudendal nerve stimulation device. Provide a catheter for. The catheter comprises a catheter body having a distal end, a proximal end, and a lumen for delivering fluid from the proximal end to the distal end. The catheter body is typically positioned at or near the distal end of the catheter body, typically positioned to measure pressure in the bladder when the catheter is in place in the urethra. Includes a first pressure sensor. The catheter may further include at least one electrode located on the catheter body at a location proximal to the distal end of the catheter. In particular, this at least one electrode is positioned on the catheter so that it lies close to the urethral sphincter when the catheter is properly placed in the urethra. Thus, the catheter typically delivers fluid through the catheter lumen to the bladder, measures the pressure in the bladder using a first pressure sensor, and delivers an electric current to the urethral nerve. Can be used to stimulate the bladder and contract and / or open the urethral sphincter muscle by appropriately applying a low frequency and / or high frequency current through an electrode located near the urethral sphincter muscle. ..

Screening catheters typically mimic actual therapeutic protocols that apply both high-frequency and low-frequency stimulation signals simultaneously or at about the same time, relaxing the sphincter muscles and simultaneously contracting the bladder, resulting in urination. obtain. In an alternative embodiment, a high frequency current may be delivered first to open the sphincter muscles, followed by a low frequency current to contract the bladder after a selected period of time. In yet another alternative embodiment, a low frequency current is first delivered to constrict the bladder, generate more pressure for more complete excretion, followed by a low frequency after a selected period, and the urethral sphincter muscle. May be opened to allow excretion to begin.

In certain embodiments, the catheter of the invention further comprises at least a second electrode on the catheter body located in the vicinity of the first electrode, typically spaced proximal to the distal end of the catheter body. obtain. In these embodiments, the first and second electrodes are typically connected to different current sources capable of delivering a low frequency current to contract the bladder and a high frequency current to open the urethral sphincter. Can be configured. Suitable low frequency currents that result in bladder contraction are in the range of about 15 Hz to 50 Hz and may be accompanied by amperes below 15 mA and voltages of 40 V to 60 V. Also, in one or more embodiments, the first and second electrodes deliver current into the tissue at a selected depth, stimulating the pudendal nerve, with minimal effect on the surrounding tissue. As such, a pair of bipolar electrodes may be provided that may be separated by a selected distance.

In yet another embodiment, the catheter of the invention may further include a second pressure sensor on the catheter body at a location proximal to the distal end of the catheter body. Normally, the second pressure sensor has the first and second electrodes and the second pressure sensor adjacent to or in the urethral sphincter when the distal end of the catheter is in the patient's bladder. It may be located in close proximity to the first and optionally the second electrode, eg, between the first and second electrodes, so that it can be positioned as such.

Still in further embodiments, the catheter of the invention may be provided with a deployable anchor, such as a balloon, similar to that found on conventional Foley catheters, and is positioned on the catheter body. When the anchor is deployed to the neck of the bladder, the anchor is positioned on the catheter body so that at least one electrode, optionally a second electrode and pressure sensor, is adjacent to the pudendal nerve and the urethral sphincter.

In a third aspect, the invention is operably connectable to a catheter as described above, which opens a low frequency current for contracting the patient's bladder and the patient's urethral sphincter. Provides a system that delivers high frequency currents for, equipped in combination with a controller. Normally, the controller may deliver a low frequency current to the first electrode and a high frequency current to the second electrode. The controller is further configured to present data from a first pressure sensor to indicate bladder pressure and / or data from a second pressure sensor to indicate sphincter compression pressure or force. It may have or be connected to a larger display or screen.
The present invention provides, for example,:
(Item 1)
A method for screening a patient for pudendal nerve treatment to treat urethral dysfunction in the patient.
A step of introducing a catheter through the patient's urethra into the patient's bladder, wherein the catheter comprises at least one electrode and at least one lumen.
A step of locating at least one electrode on the catheter at a location within the urethra, the step of delivering an electric current to the patient's pudendal nerve.
The step of delivering the fluid into the patient's bladder through the catheter,
A step of delivering an electric current to the pudendal nerve through the at least one electrode, wherein the electric current is a low frequency current for contracting the bladder of the patient and a high frequency current for opening the urethral sphincter muscle of the patient. Steps, including at least one of them,
The step of measuring information about the physiological response generated in response to the delivered current,
Steps to utilize the information about the generated physiological response to assess the patient's response to the delivered current, and
Including, how.
(Item 2)
The method of item 1, wherein the at least one electrode comprises first and second electrodes positioned to deliver an electric current to the pudendal nerve.
(Item 3)
The method of item 2, wherein the first electrode delivers a low frequency current and the second electrode delivers the high frequency current.
(Item 4)
3. The method of item 3, wherein the catheter is positioned such that each of the first and second electrodes is positioned in the vicinity of the urethral sphincter.
(Item 5)
The catheter comprises at least two lumens, the first lumen filling the bladder and the second lumen being delivered for the low frequency to contract the bladder. , The method of item 1, for excretion of fluid from the bladder.
(Item 6)
The method of item 1, wherein the bladder is filled to a target pressure.
(Item 7)
The method of item 1, wherein the target pressure is in the range of about 10 to 45 mmHg or about 10 to 20 mmHg.
(Item 8)
The method of item 1, wherein the bladder is filled to a target volume.
(Item 9)
8. The method of item 8, wherein the target volume is in the range of about 50-200 ml.
(Item 10)
The method of item 1, wherein the high and low frequency currents are delivered at about the same time.
(Item 11)
The method of item 1, wherein delivery of the high frequency current is initiated prior to delivery of the low frequency current.
(Item 12)
The method according to item 1, wherein the low frequency current is in the range of about 15 Hz to 50 Hz.
(Item 13)
The method of item 1, wherein the high frequency current is in the range of about 4-10 kHz.
(Item 14)
Item 1. The catheter is positioned to block the opening of the patient's bladder so that when the bladder is contracted, the excreted fluid substantially flows through the lumen within the catheter. The method described.
(Item 15)
14. The method of item 14, further comprising measuring the flow rate of the excreted fluid flowing through the catheter.
(Item 16)
14. The method of item 14, wherein the catheter comprises an inflatable balloon or other means for blocking the opening of the patient's bladder.
(Item 17)
The method of item 1, wherein the fluid flowing from inside and outside the bladder through the catheter does not substantially affect the measurement of the information regarding the generated physiological response.
(Item 18)
17. The method of item 17, wherein the unaffected information comprises at least one of bladder pressure, urethral sphincter pressure, or urethral flow rate.
(Item 19)
17. The method of item 17, wherein the lumen of the catheter has sufficient radial rigidity such that the force from the pressure of the fluid in the catheter is not substantially transmitted to the outside of the catheter.
(Item 20)
The method of item 1, wherein the information about the generated physiological response is used to regulate the characteristics of the high frequency or low frequency current.
(Item 21)
20. The method of item 20, wherein the characteristic is the frequency, magnitude, or waveform shape of the high frequency or low frequency current.
(Item 22)
20. The method of item 20, wherein the adjustment comprises at least one adjustment or fine adjustment of the high frequency or low frequency current.
(Item 23)
22. The method of item 22, wherein the fine-tuning comprises adjusting the properties in an amount less than about 5 percent.
(Item 24)
22. The method of item 22, wherein the adjustment comprises adjusting the property in an amount in the range of about 5 to about 25 percent.
(Item 25)
22. The method of item 22, wherein the high frequency or low frequency current characteristics are used to enable or ameliorate the patient's urethral function.
(Item 26)
The method of item 1, wherein the urethral dysfunction is a reduction in the ability to spontaneously control urination.
(Item 27)
The method of item 1, wherein the measured information is bladder pressure.
(Item 28)
27. The method of item 27, wherein the bladder pressure is measured using a pressure sensor.
(Item 29)
27. The method of item 27, wherein the measured information further comprises a contraction pressure of the urethral sphincter.
(Item 30)
29. The method of item 29, wherein the bladder pressure and the urethral sphincter contraction pressure are measured simultaneously.
(Item 31)
28. The method of item 28, wherein the bladder pressure sensor is located on the catheter or the distal end of the catheter.
(Item 32)
28. The method of item 28, wherein the catheter is advanced to position the pressure sensor inside the bladder.
(Item 33)
The method of item 1, wherein the measured information is the contraction pressure of the urethral sphincter.
(Item 34)
33. The method of item 33, wherein the contraction pressure is measured using a pressure sensor.
(Item 35)
34. The method of item 34, wherein the pressure sensor is positioned adjacent to the urethral sphincter.
(Item 36)
The method of item 1, wherein the measured information comprises a urethral flow velocity.
(Item 37)
36. The method of item 36, wherein the high frequency or low frequency current characteristics are adjusted to achieve a target urethral flow velocity.
(Item 38)
37. The method of item 37, wherein the characteristic is the frequency or magnitude of the high frequency or low frequency current.
(Item 39)
37. The method of item 37, wherein the target urethral flow rate is in the range of about 9-21 ml / min for male patients and 15-18 ml / min for female patients.
(Item 40)
A catheter for screening patients for pudendal nerve treatment,
A catheter body having a distal end, a proximal end, a lumen for delivering fluid from the proximal end to the distal end and having a first lumen, said lumen having a distal opening. , The catheter body and
A first pressure sensor located on the catheter body in the vicinity of the distal end of the catheter body and measuring the patient's bladder pressure.
A second pressure sensor, located proximal to the distal end of the catheter body, to measure the patient's urethral sphincter pressure.
With at least one electrode located on the catheter body at a location proximal to the distal end of the catheter and delivering an electric current to the pudendal nerve.
Equipped with
The catheter body is configured to advance through the patient's urethra and position the first pressure sensor and the distal opening of the lumen within the patient's bladder.
When the catheter is so positioned, the first lumen does not significantly affect the simultaneous measurement of the patient's bladder pressure or urethral sphincter pressure by the first or second pressure sensor. Configured to allow the flow of said fluid into the bladder,
catheter.
(Item 41)
40, wherein the first lumen has sufficient radial stiffness or hoop strength to minimize the transmission of force from fluid pressure from the inside of the lumen to the outside of the catheter body. Catheter.
(Item 42)
41. The catheter of item 41, wherein the first lumen comprises a reinforced braid configured to minimize the transmission of force from fluid pressure from the inside of the lumen to the outside of the catheter body. ..
(Item 43)
40. The catheter according to item 40, wherein the catheter body comprises a second lumen for the flow of the fluid from the bladder to the outside of the patient's body.
(Item 44)
The catheter according to any one of items 40 or 43, wherein the radial stiffness of the first or second lumen is in the range of about 50-100 N / mm.
(Item 45)
40. The catheter according to item 40, wherein the catheter is adapted to be positioned within the male urinary tract.
(Item 46)
The catheter according to item 45, wherein the second sensor has a length of about 2 cm and is located about 2.5 to 3.5 cm from the distal end of the catheter.
(Item 47)
40. The catheter according to item 40, wherein the catheter is adapted to be positioned within the female urinary tract.
(Item 48)
47. The catheter of item 47, wherein the second sensor has a length of about 1.5 cm and is located about 1.8 to 2.8 cm from the distal end of the catheter.
(Item 49)
40. The catheter according to item 40, wherein the catheter body comprises an elastomer, silicone, or polyurethane, PTFE, polyethylene, or PET.
(Item 50)
40. The catheter of item 40, wherein the at least one electrode comprises a pair of bipolar electrodes.
(Item 51)
50. The catheter of item 50, wherein the pair of bipolar electrodes is located at a distance selected to target the depth of current delivered within the tissue to the pudendal nerve.
(Item 52)
Further comprising at least a second electrode on the catheter body, located proximal to the distal end, the first and second electrodes are configured to be connected to different current sources. The catheter according to item 40.
(Item 53)
Each of the first and second electrodes and the second pressure sensor are positioned so that they can be in the patient's urethral sphincter when the distal end of the catheter is in the patient's bladder. 52. The catheter according to 52.
(Item 54)
40. The catheter of item 40, further comprising a deployable anchor positioned on the catheter body, wherein the at least one electrode may be adjacent to the pudendal nerve when the anchor is deployed to the neck of the bladder.
(Item 55)
54. The catheter of item 54, wherein the deployable anchor is located near the distal end of the catheter body.
(Item 56)
54. The catheter according to item 54, wherein the deployable anchor comprises an inflatable balloon.
(Item 57)
A system for screening patients for pudendal nerve treatment to treat urethral dysfunction in patients.
The catheter according to item 52 and
A low frequency current that can be connected to the first and second electrodes to contract the patient's bladder to the first electrode and a high frequency current to open the patient's urethral sphincter. With the controller delivered to the second electrode,
The system.
(Item 58)
The controller further comprises a pressure display that is connectable to at least one of the first or second pressure sensors and displays at least one of the bladder pressure or the urethral sphincter contraction pressure. , Item 57.
(Item 59)
58. The system of item 57, wherein the controller is further configured to deliver paresthesia blocking currents to block or reduce paresthesia resulting from low or high frequency currents.
(Item 60)
59. The system of item 59, wherein the catheter body comprises a third electrode for delivery of the paresthesia blocking current.
(Item 61)
The system of item 59, wherein the paresthesia blocking current has a frequency in the range of about 3 kHz to 20 kHz.

Further details of these and other embodiments and aspects of the invention will be fully described below with reference to the accompanying drawings.

FIG. 1 is for selectively stimulating the pudendal nerves obtained from U.S. Patent Publication No. 2014/0249595 (incorporated herein above by reference in its entirety) to control urination. The prior art system is illustrated. In particular, FIG. 1 depicts a three-channel system for stimulating the pudendal nerve or its branches. The pulse generator 10 is depicted as having three output channels. Wire leads 12 and 13 are attached to electrodes 14 and 15, which are placed around the pudendal nerve 20. The electrode 15 is shown distal to the electrode 14. In the context of the method, which comprises the steps of blocking the EUS and / or the anal sphincter and stimulating or blocking contractions in the bladder and / or rectum, the electrode 14 is used to stimulate or block contractions in the bladder and / or rectum. On the other hand, the electrode 15 will be used to block the EUS or anal sphincter. If necessary, the wire conductor 16 is placed around the pudendal nerve on the other side of the body and attached to another electrode (not shown in FIG. 1) that blocks the pudendal nerve on the opposite side. The pulse generator 10 is shown embedded beneath the skin 40. The output parameters of the pulse generator 10 can be controlled via a wired interface, but preferably any suitable radio protocol such as radio frequency, IEEE802.11a / b / g, Bluetooth®. Controlled by wireless transmission, which can be carried using. Therefore, the external controller 30 is depicted for communicating with the pulse generator 10. The external controller 30 is depicted as having a display 32 such as an LCD, LED, or OLED display, and a keypad 34 for driving data into the external controller 30. The external controller is depicted to transmit the radio transmission 36 to the pulse generator 10, but in another embodiment the data is transferred from the external communicator 30 to the pulse generator 10 and vice versa. Allows monitoring of one or more parameters of the pulse generator 10, including, but not limited to, output signal characteristics (eg, frequency, amplitude, etc. as outlined above) and battery strength. can. The activity of the pulse generator 10 and the external controller 30 is typically controlled by a microcontroller and the software / firmware installed on the pulse generator 10 and the external controller 30 hardware implements the tasks described. , For example, but may be used to provide a GUI (graphical user interface) for the display 32 that facilitates the use of the system. Both the pulse generator 10 and the external controller 30 include any suitable electrical and electronic components such as microprocessors, memories (eg, RAM, ROM, flash memory, etc.), connectors, batteries, power transformers, amplifiers, etc. Activities may be implemented, including. FIG. 2 illustrates an exemplary embodiment of a test catheter constructed according to the principles of the invention. FIG. 3 illustrates the test catheter of FIG. 2 that is placed in the patient's urethra and for performing the test protocol according to the method of the invention. FIG. 3a is an enlarged view of FIG. 3 showing the positioning of the test catheter electrode within the patient's urethral sphincter for stimulating the patient's pudendal nerve. 4a and 4b illustrate embodiments of a test catheter with a second lumen for fluid flow from the bladder to the outside of the patient. 4a and 4b illustrate embodiments of a test catheter with a second lumen for fluid flow from the bladder to the outside of the patient. FIG. 5 illustrates an embodiment of a bipolar electrode for use as a pudendal nerve stimulating electrode for use with an embodiment of a test catheter.

Detailed Description of the Invention An embodiment of the invention is to test a patient in which spontaneous control of urethral function is not possible and / or diminished, and the tested patient controls bladder excretion. Provides devices, systems, and methods for ascertaining whether they will enable or benefit from pudendal nerve stimulation therapy. Such patients may include patients paralyzed due to spinal cord injury and / or patients with multiple sclerosis or other motor neuron disease. Certain embodiments of the invention include US Patent Application Publication No. 2014/0249595 (incorporated herein by reference above) and a co-pending book filed on January 19, 2016. By an implantable device for providing bladder control, such as that described in Applicant-owned US Provisional Application No. 62 / 280,639, which is incorporated herein by reference in its entirety. It provides a device that mimics what is provided, and the methods of the invention allow testing of bladder stimulation protocols.

Referring here to FIGS. 2, 3a, 4a-4b, and 5, the embodiment of the test catheter 200 stimulates the catheter body 202, which has a distal end 204 and a proximal end 206, and a pudendal nerve PN, and bladder. It comprises at least two electrodes 228 and 230 for inducing or otherwise producing physiological responses involved in the micturition process such as contraction of the urethral sphincter and relaxation of the urethral sphincter. The catheter body is known in the art, including, for example, HDPE (High Density Polyethylene), LDPE (Low Density Polyethylene), Pebax® Polymers, PTFE, Silicone, Polyurethane, or other elastomers known in catheter technology. It may be made from various flexible biocompatible polymers of. The lumen 210, which has port 208 at the distal end of the catheter body 202, is fluid connectable to the fluid source 212 through port 226 on the proximal hub 224 of the catheter. As shown in FIGS. 4a and 4b, in an alternative or additional embodiment, the test catheter 200 is also for fluid flow from the patient's bladder B to the outside of the body, as described in more detail below. It may include a second lumen 211 to promote excretion and allow measurement of urinary flow rate. In various embodiments, the fluid source 212 is a physiological saline solution, water, when the distal end 204 of the catheter 200 is present in the bladder B, as illustrated in FIG. 3a, which will be described later herein. Or any other suitable pressurized liquid can be delivered to the patient's bladder through the lumen 210, a pressure control pump, a suspended fluid bag (eg, a bag of premixed physiological saline solution), or any. Other conventional fluid sources may be accommodated.

Referring here to FIGS. 3a and 5, electrodes 228 and 230 may include various biocompatible conductive metals and other conductive materials known in medical devices and electrophysiological techniques. In various embodiments, the electrodes 228 and 230 may correspond to different ring electrodes and have a selectable width selected to achieve the desired penetration depth through the urethral sphincter tissue to the pudendal nerve, eg, 1. It may have up to 10 mm. The spacing S between the electrodes 228 and 230 is preferably chosen to position these electrodes inside the urethral sphincter US, as shown in FIG. 3a.

As shown in FIG. 5, in alternative or additional embodiments, the pudendal nerve stimulation electrodes 228 and 230 may correspond to individual pairs 242 of bipolar electrodes 240. Each pair of bipolar electrodes 242 includes first and second electrodes 243 and 244 through which alternating current or other current may flow in between. The distance or gap 245 between each individual electrode 243 and 244 of the bipolar pair 240 controls the penetration depth of the stimulus current flow between them and selectively avoids any surrounding tissue while selectively selecting the pudendal nerve. It may be selected to be targeted. Longer distances tend to produce deeper penetrations, while shorter distances tend to be shallower. In various embodiments, the gap 245 can range from about 1-5 mm, but longer and shorter gaps are also contemplated. This gap may also be selected depending on whether the current is a high frequency or low frequency current, as described herein.

According to one or more embodiments, the catheter body 202 and / or the lumen 210 or the other lumen 211 is a catheter using sensor sensors 214 and 232 or another sensor for fluid pressure in individual lumens. It may be sufficiently rigid (eg, radial rigidity or stiffness) and / or to prevent it from significantly affecting pressure measurements of bladder pressure and / or contraction pressure of the urinary tract sphincter by 200. It may have sufficient hoop strength. By "significantly" is meant an effect on pressure below about 10%, more preferably below about 5%, even more preferably below about 1%. More specifically, a lumen of one or more of the catheter 200 (here, the lumen wall is also meant) is preferably inside the lumen, which can affect the measurement by the catheter 200. Rigid enough to minimize or prevent the transmission of force from the fluid pressure to the outside of the catheter. Desirably, the transmitted force is less than 0.2 pounds, more preferably less than 0.05 pounds, and even more preferably less than 0.01 pounds. Similarly, lumens 210, 211 also affect pressure measurements and / or narrow the adjacent lumen and significantly affect the flow velocity through the adjacent lumen, from the lumen to the other. Rigid enough to minimize pressure transfer. In other words, these lumens prevent hydrostatic pressure crosstalk from one lumen to the next and prevent pressure within one lumen from constricting adjacent lumens. It is rigid enough for it. They are also rigid enough to maintain their shape from the application of force to adjacent lumens or when the catheter body is positioned and bent in the patient's urinary tract. However, preferably, the catheter 200 and the catheter body 201, as a whole, may remain sufficiently extensible to advance and be manipulated within and through the intended patient body structure for clinical use scenarios. In a specific embodiment, the catheter lumens 210 and 211 are such that any change in pressure or flow velocity within one lumen resulting from pressure or pressure changes in adjacent lumens is preferably less than about 5%. It has sufficient stiffness or hoop stress so that it will preferably remain below 2%, and even more preferably 1%. In various embodiments, such stiffness or hoop strength can be achieved by any one or more of the following: (1) Catheter material choices, (2) Catheter / lumen dimensions, (3) Use of reinforced braids (inside and outside the lumen), and / or (4) Internal reinforced lumens. In various embodiments, the radial stiffness of any one of the lumens 210, 211 or other lumens of the catheter 200 (also referred to herein as radial stiffness) is about 1. It can be in the range of about 100 N / mm, more preferably in the range of about 20 to about 100 N / mm, even more preferably in the range of about 50 to about 100 N / mm, and the specific embodiment is 5, 10, 20, 25, 30, 40, 45, 50, 55, 60, 70, 75, 80, 90, and 95 N / mm, while the hoop strength is from about 0.25 to 5 pounds. It can preferably be in the range of about 0.5-5 pounds, even more preferably about 1-10 pounds, and specific embodiments are 0, 5, 1, 2, 2, 5, 3, It is a force of 4, 5, 6, 7, 8 and 9 pounds.

In one or more embodiments, the catheter 200 may also include a first pressure sensor 214, typically located at or near the distal end 204 of the catheter body 202, but for a pressure sensor. It should be understood that other positions on the body of the catheter are also intended. The first pressure sensor 214 is typically a variety of solid state pressure transducers known in the art, including a solid state pressure transducer suitable for measuring pressure in the bladder (eg, a strain gauge based on a microelectromechanical system). Solid-state strain gauges), typically in the range 0-50 mmHg, but other ranges are also considered. Normal bladder pressure is in the range of 0-10 mmHg, and sometimes 0-20 mmHg, but the methods of the invention may rely on delivery and measured pressures above normal bladder pressure. The bladder pressure read by the transducer 214 may be displayed on the read information 218 on the controller 216, or using Bluetooth® or Bluetooth® LE or other radio communication protocol and / or radio means. Then, it may be wirelessly transmitted to an external display. The reading information 218 may be a dedicated LCD, LED, or other numerical or analog reading information, or may be a display screen, optionally a part of a touch screen display. The catheter 200 optionally stabilizes the catheter body 202 and properly positions the electrodes 228 and 230 in or near the patient's urethral sphincter, as described in more detail with respect to FIG. 3a below. It may include a distal anchor such as an inflatable balloon 220 that can be positioned within the bladder. The second pressure transducer 232 may often be provided in the vicinity of the electrodes 228 and 230 to allow measurement of the contractile pressure of the urethral sphincter. The pressure sensors 214 and 232 and the electrodes 228 and 230 may be connected by wires or cables 238 that pass through the catheter body and connect the electronic components to the controller 216. They may also be wireless devices configured to communicate with the controller 216 via Bluetooth® or other wireless protocol. The balloon 220 can be inflated by a conventional inflatable source 222 of the type normally used in conjunction with a Foley catheter. The sphincter pressure measured by the second pressure transducer 232 may be shown on the second display element 234 on the controller 216, or also on a conventional touch screen or other display on the controller. You may. The controller 216 may also typically include a user interface 236. According to various embodiments, the user interface 236 may be a touch screen (which can be the same touch screen for displaying all data), a keyboard, a joystick, or any other conventional user interface. Often, this may be directly or wirelessly coupled to the controller.

Referring now to FIG. 3, the catheter 200 of FIG. 2 allows the anchor balloon 220 to be positioned within the patient's bladder B and rested above or within the bladder neck BN of the patient's urethra U. May be introduced through. The dimensions for the catheter are that electrodes 228 and 230 and a second pressure sensor 232 are generally located within the patient's urethral sphincter US, stimulating the pudendal nerve PS and sitting as best shown in FIG. 3a. May be selected to do so.

In one or more embodiments, adaptation of the length and other dimensions of the catheter 200 and its components can be made with respect to the gender of the patient. For example, in the case of a catheter 200 adapted for the male urinary tract, a second sensor 232 for measuring urethral contraction pressure is a catheter approximately 2.5 cm to 3.5 cm proximal to the distal end 204 of the catheter. It may be located on the body 201 and extend to about 2.0 cm of urethral length. In the female version of the catheter, the sensor 232 is located approximately 1.8-3 cm proximal to the distal catheter end 204 and extends to approximately 1.5 cm of urethral length.

At the location shown in FIG. 3, the catheter 200 first fills the bladder and pressurizes to the desired target level, typically from about 10 mmHg to about 45 mmHg, to a preferred range of about 10 to about 20 mmHg. Alternatively, it may be used to introduce a fluid such as saline into the bladder B. In a related embodiment, the catheter 200 may be used to fill the bladder, for example, to a target volume in the range of about 50-200 ml. As used herein, the term "about" means within ± 10% of the stated value with respect to parameters, measurements, dimensions, properties, physical properties, and equivalents. Once bladder B is filled to the desired pressure and / or with the desired volume of fluid, a low frequency bladder contraction current, typically having a frequency of about 15 Hz to about 50 Hz, stimulates the pudendal nerve PN. However, it may be applied through the first electrode 228 so as to cause contraction of the bladder. Simultaneously or approximately simultaneously (eg, within about 0.2 seconds in this case), a high frequency urethral sphincter relaxation current may be applied by the second electrode 230 to cause relaxation and opening of the urethral sphincter. In some embodiments, the high frequency current allows the urethral sphincter muscles to relax and completely open before the bladder contracts from the low frequency current, and the fluid resistance in the urethra to the bladder contraction causes the bladder. May be initiated at a selected time prior to the low frequency current (eg, about 0.2-2 seconds) so that is minimized before it begins to contract. Typically, high frequency currents have frequencies above 4 kHz, amperes are below about 15 mA, voltages range from 40 V to 60 V, and specific ranges for high frequency currents are 4. -10 kHz, 4-15 kHz, and 4-20 kHz can be included, but other ranges are still contemplated. When high and low frequency currents are applied, bladder contraction and urethral sphincter opening indicate that the patient urinates (also referred to herein as excretion) through the annular urethral space surrounding the catheter 200. to enable.

In an alternative or additional embodiment, a second high frequency current, typically above 1 kHz, is caused by the delivery of currents to the pudendal nerve by the electrodes 228 and 230, any stinging, burning, numbness, or. It may be delivered to the pudendal nerve by the catheter 200 to block or otherwise attenuate the associated sensation (known as paresthesia). Described herein as a paresthesia blocking current, the current may be delivered by either or both of the electrodes 228 and 230, or a third electrode on or outside the catheter 200 (not shown). May be delivered by. Desirably, the paresthesia blocking current is generated by a different current source than that used to generate the first two currents (eg, bladder contraction and sphincter relaxation currents). In various embodiments, the paresthesia blocking current may have frequencies in the range of 1.5 kHz to 100 kHz, more preferably in the range of about 3 kHz to 20 kHz. In one or more embodiments, the waveform of the paresthesia blocking current is a two-phase pulse with a pulse width in the range of 10 μsec to 333 microseconds, more preferably in the range of about 30-35 μsec. It may correspond. The amplitude can vary from about 1 mA to about 4 mA and the nominal value is about 2.5 mA. These and other properties of sensory anomaly blocking currents are patient feedback on perceived sensory abnormalities and / or bladder pressure, the urethra, in a manner similar to current regulation for contracting the bladder and relaxing the urethral sphincter. It can be adjusted or fine-tuned or otherwise adjusted based on one or more of the measurements of sphincter contraction pressure and urethral flow velocity. Thus, embodiments of the invention implant the pudendal nerve stimulating device such that the patient has better outcome than if the pudendal nerve stimulating device was pre-programmed with standard paresthesia blocking currents. Previously, it can be used to optimize paresthesia blocking current.

See here in FIGS. 4a and 4b. In an alternative or additional embodiment, the catheter 200 comprises an additional lumen or other channel 211 and excretes or urinates through the lumen 211 while the catheter 200 is positioned at the desired location in the patient's urinary tract. Can be promoted. Lumen 211 can include one or more distal openings 211o for fluid flow from the bladder into the catheter. Desirably, the opening 211o is so far away from the catheter that the opening 211o is slightly above the bladder neck and anchor device 220 to facilitate fluid flow into the catheter and complete excretion of the bladder. Positioned at a selected distance proximal to position 214. Again, as discussed herein, the lumen 211 is sufficiently radial rigid to maintain its shape when the catheter is flexed and / or receives fluid pressure from the lumen 210. Can have a degree (eg, through the use of reinforcing braids). In use, an embodiment of a catheter having a dedicated lumen 211 for fluid flow from the bladder allows all urine flow to proceed through the catheter while the pudendal nerve is stimulated to induce urination by the electrode 230. As the flow velocity or total volume can be measured, it facilitates a more accurate measurement of urinary flow velocity. Measurements are made manually (by timing and collecting excreted fluid) or using a flow sensor, which can be an external sensor, located over the catheter or at the proximal end of the catheter. Can be done. According to some embodiments, the catheter 200 may include its own flow sensor 235, which may be located in or around the lumen 211 or the catheter body 20. The flow sensor 235 may also be operably coupled to the controller 216 to convey information about urine flow to the controller. The flow sensor 235 may accommodate a variety of electromagnetic, optical, aneometric, and acoustic flow sensors known in the art, including various solid state flow sensors. In a further specific embodiment, the measured urine flow velocity is a high and low frequency current, including, for example, amplitude (either voltage and / or current), frequency, pulse width, as described herein. It may be used to regulate the properties of one or more of the above. Suitable target urine flow rates for men and women are shown in Table 1. In various embodiments, the fluid resistance within the lumen 211 (including for the individual catheter 210) at the flow velocity and bladder pressure corresponding to those typical during urination is pre-measured and catheterized. It can be stored in a memory device that is shipped with and configured to be operably coupled to the controller 216. Alternatively, they may be calculated for a standard diameter lumen 211 and stored in controller 216. Such fluid resistance then translates the fluid flow velocity through the lumen 211 resulting from induced bladder excretion into the rate that would be expected through the urethra in the case of a catheter 200 that is not positioned within the patient's urinary tract. Can be used for.

As discussed herein, in these and related embodiments, the first lumen 210 (including the lumen wall 210w) varies during fluid flow for the lumen 210 to fill the bladder. Under pressure, it does not cause any significant radial deformation of the diameter of the additional lumen and a significant amount (eg, less than 10%, more preferably less than 5%, even more preferably less than 1%). ) Sufficient radial rigidity or can be otherwise reinforced to reduce the urine flow velocity through the second (urinary outflow) lumen. In addition, the second pressure transducer 232 is preferably configured to measure the decrease in urethral sphincter pressure as the sphincter relaxes. Observation / measurement of urine passage and optionally reduction of sphincter pressure indicates that the patient responds in favor of pudendal nerve stimulation and is a good candidate for a complete implantation procedure. This and other information about the physiological response to the delivered high and low frequencies or other currents can be used as a basis for assessing the effectiveness of genital treatment.

In one or more embodiments, various information collected using catheter 200 or other measuring means associated with the physiological response generated from pudendal nerve treatment treats the patient's urethral dysfunction. It can be used as a criterion for assessing the effectiveness of treatment when urinating (eg, being able to initiate and control urination). Such information may also be used to adjust the properties of one or more of the high and low frequency currents to optimize pudendal nerve treatment for a particular patient. According to various embodiments, such criteria can include one or more of urinary flow velocity, decreased urethral sphincter pressure, and increased bladder pressure. For urine flow, a minimum flow rate within 0-30% of the values shown in Table 1 may be used. For urethral sphincter pressure, a pressure reduction of about 50, 60, 70, 75, 80, 90, or 95% (other values are also considered) may be used. Further, in the case of bladder pressure, an increase in amount of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 95% (other values are also considered) may be used.

In certain embodiments, one or all of the urinary / excretory flow rate, decreased urethral sphincter pressure, and increased bladder pressure are subsequently implanted at high frequencies and low frequencies to be used within the pudendal treatment device. It may be used to preselect both frequency and current. In particular, high and low frequencies are "adjusted" (roughly) while observing or tracking changes in urinary flow rate to identify those settings that result in selection and / or maximum urinary flow rate and / or shortest micturition duration. May be fine-tuned) or "fine-tuned" (finely adjusted). Specific adjustments may be made at one or more of the high and low frequency currents, including frequency, wave current or voltage, and wave shape. In particular, the adjustment may be made at the peak amplitude of the current or voltage as well as the RMS amplitude. Also, different waveforms may be employed, including, for example, sine, square, and sawtooth waves. Also, in one or more embodiments, the waveform may be in the form of a two-phase pulse with a selectable pulse width, eg, 1-100 ms.

Rough adjustments may incorporate changes that are in the range of about 5 to about 25%, while fine adjustments may be less than about 5%. For example, in one particular embodiment, one or more of the bladder pressure and urinary flow velocity adjusts and fine-tunes the low frequency current for a particular patient and is the choice for a particular patient. And / or can be used to generate an optimized urinary flow rate and / or an optimized micturition sequence (eg, timing of bladder contraction and urethral sphincter relaxation). In another embodiment, one or both of the urinary flow velocity and the urethral sphincter pressure adjust and fine-tune the high frequency current, and the selected and / or optimized urinary flow velocity and / or optimized for a particular patient. It can be used to generate a urinary sequence (eg, timing of bladder contraction and urethral sphincter relaxation). Thus, not only can candidates for pudendal nerve stimulation treatment to enable or improve urethral function be selected, but also urethral function achieved by embodiments of pudendal nerve stimulation treatment is also an electrode, It can be optimized on a patient-by-patient basis before having any embedded device such as a wire, controller, etc. This, in turn, should improve the final clinical outcome of candidate patients for pudendal nerve stimulation treatment, and also remove and / or re-implant electrodes and other components of the pudendal nerve stimulation system. Reduce the risk of morbidity and mortality from need.

The above description of the various embodiments of the invention are presented for purposes of illustration and illustration. This is not intended to limit the invention to the disclosed precise forms. Many modifications, variations, and refinements are apparent to those of skill in the art. For example, embodiments of the device can be sized and otherwise adapted for different pediatric and different veterinary applications. Also, one of ordinary skill in the art will be able to recognize or confirm a number of equivalents of the specific devices and methods described herein using experiments that are only routine. Such equivalents are considered to be within the scope of the invention and are covered by the appended claims below.

Elements, properties, or actions from one embodiment can be easily recombined or substituted with one or more elements, properties, or actions from other embodiments, and many additional additions within the scope of the invention. Embodiments can be formed. In addition, the elements illustrated or described for combination with other elements can, in various embodiments, exist as stand-alone elements. Therefore, the scope of the invention is not limited to the details of the embodiments described, but instead is limited only by the appended claims.

Claims (17)

A catheter for screening patients for pudendal nerve treatment,
A distal end, a proximal end, a first lumen for delivering fluid from the proximal end to the distal end, the first lumen having a distal opening, and the patient. A catheter body having a second lumen for fluid flow from the bladder to the outside of the patient,
A first pressure sensor located on the catheter body in the vicinity of the distal end of the catheter body and measuring the bladder pressure of the patient.
A second pressure sensor, located proximal to the distal end of the catheter body, to measure the patient's urethral sphincter pressure.
Located on the catheter body at a location proximal to the distal end of the catheter, it comprises at least one electrode that delivers an electric current to the pudendal nerve.
The catheter body is advanced through the patient's urethra and is configured to position the first pressure sensor and the distal opening of the catheter within the patient's bladder.
When the catheter is so positioned, the first lumen does not significantly affect the simultaneous measurement of the patient's bladder pressure or urinary sphincter pressure by the first pressure sensor or the second pressure sensor. In addition, the second lumen is configured to allow fluid to flow into the patient's bladder so that the excreted fluid flows out of the patient through the second lumen. Is configured to enable
The catheter is configured to measure information about the physiological response generated in response to the delivered current, the information being used to generate excretory fluid flow information in the second lumen. Including the flow velocity of the excreted fluid flowing through,
The excretory fluid flow information is utilized to assess the physiological response to the delivered current, the catheter. The first lumen has sufficient radial stiffness or hoop strength to minimize the transmission of force from fluid pressure from the inside of the first lumen to the outside of the catheter body. Item 1. The catheter according to item 1. 2. The first lumen comprises a reinforcing braid configured to minimize the transmission of force from fluid pressure from the inside of the first lumen to the outside of the catheter body. The catheter described. The catheter according to claim 1 , wherein the radial rigidity of the first lumen or the second lumen is in the range of 50 to 100 N / mm. The catheter according to any one of claims 1 to 4, wherein the catheter is adapted to be positioned in the male urinary tract. The catheter according to claim 5, wherein the second pressure sensor has a length of 2 cm and is located 2.5 to 3.5 cm from the distal end of the catheter. The catheter according to any one of claims 1 to 6 , wherein the catheter is adapted to be positioned in the female urinary tract. The catheter according to claim 7, wherein the second pressure sensor has a length of 1.5 cm and is located 1.8 to 2.8 cm from the distal end of the catheter. The catheter according to any one of claims 1 to 8 , wherein the catheter body comprises an elastomer, silicone, or polyurethane, PTFE, polyethylene, or PET. The at least one electrode comprises a pair of bipolar electrodes, the pair of bipolar electrodes being positioned at a distance selected to target the pudendal nerve to the depth of current delivered within the tissue. Item 5. The catheter according to any one of Items 1 to 9 . The at least one electrode is a plurality of electrodes, the plurality of electrodes comprising at least a first electrode and a second electrode on the catheter body located proximal to the distal end. The first electrode and the second electrode are configured to be connected to different current sources, and each of the first electrode and the second electrode and the second pressure sensor are of the catheter. The catheter according to any one of claims 1 to 10 , wherein when the distal end is in the patient's bladder, it is positioned so that it can be in the patient's urinary sphincter muscle. 13 . The catheter according to one item. 12. The catheter according to claim 12, wherein the deployable anchor is located near the distal end of the catheter body and the deployable anchor comprises an inflatable balloon. A system for screening patients for pudendal nerve treatment to treat urethral dysfunction in patients.
The catheter according to any one of claims 1 to 13 .
The at least one electrode is a plurality of electrodes, wherein the plurality of electrodes are located at a location proximal to the distal end, at least a first electrode and a second electrode on the catheter body. The system is equipped with
A controller that is connectable to the first electrode and the second electrode, the controller delivers a low frequency current to contract the patient's bladder to the first electrode and the patient's. A controller that delivers a high frequency current to open the urethral sphincter to the second electrode.
The system. The controller further comprises a pressure display, the pressure display being connectable to at least one of the first pressure sensor or the second pressure sensor, of bladder pressure or urinary sphincter contraction pressure. 14. The system of claim 14 , displaying at least one. 15. The system of claim 14 or 15 , wherein the controller delivers a paresthesia blocking current and is further configured to block or reduce paresthesia resulting from the low frequency current or the high frequency current. 16. The system of claim 16 , wherein the catheter body comprises a third electrode for delivery of the paresthesia blocking current, the paresthesia blocking current having a frequency in the range of 3 kHz to 20 kHz.

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