U.S. patent application number 17/700415 was filed with the patent office on 2022-07-07 for systems and methods for establishing a nerve block.
The applicant listed for this patent is SetPoint Medical Corporation. Invention is credited to Michael A. FALTYS, Jacob A. LEVINE, Jesse M. SIMON.
Application Number | 20220212001 17/700415 |
Document ID | / |
Family ID | 1000006211008 |
Filed Date | 2022-07-07 |
United States Patent
Application |
20220212001 |
Kind Code |
A1 |
FALTYS; Michael A. ; et
al. |
July 7, 2022 |
SYSTEMS AND METHODS FOR ESTABLISHING A NERVE BLOCK
Abstract
A nerve cuff for establishing a nerve block on a nerve can have
a cuff body with a channel for receiving a nerve, a reservoir for
holding a drug, and an elongate opening slit extending the length
of the cuff body that can be opened to provide access to the
channel and can be closed to enclose the cuff body around the
nerve. The nerve cuff can also include an electrode for detecting
and measuring electrical signals generated by the nerve. A
controller can be used to control delivery of the drug based on the
electrical signals generated by the nerve.
Inventors: |
FALTYS; Michael A.;
(Valencia, CA) ; LEVINE; Jacob A.; (West
Hempstead, NY) ; SIMON; Jesse M.; (Los Angeles,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SetPoint Medical Corporation |
Valencia |
CA |
US |
|
|
Family ID: |
1000006211008 |
Appl. No.: |
17/700415 |
Filed: |
March 21, 2022 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
16785400 |
Feb 7, 2020 |
11278718 |
|
|
17700415 |
|
|
|
|
15406619 |
Jan 13, 2017 |
10596367 |
|
|
16785400 |
|
|
|
|
62278337 |
Jan 13, 2016 |
|
|
|
62286952 |
Jan 25, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/24 20210101; A61N
1/0556 20130101; A61M 2205/3584 20130101; A61B 5/4047 20130101;
A61N 1/3606 20130101; A61M 2202/0241 20130101; A61M 2230/08
20130101; A61B 5/4848 20130101; A61M 5/172 20130101; A61M 2005/1726
20130101; A61N 1/37205 20130101; A61B 2505/09 20130101; A61B
2562/168 20130101; A61B 5/4824 20130101; A61N 1/36071 20130101;
A61B 5/6877 20130101; A61M 39/0208 20130101; A61B 5/4839 20130101;
A61M 5/14236 20130101 |
International
Class: |
A61N 1/05 20060101
A61N001/05; A61B 5/00 20060101 A61B005/00; A61N 1/372 20060101
A61N001/372; A61N 1/36 20060101 A61N001/36; A61M 5/172 20060101
A61M005/172; A61M 39/02 20060101 A61M039/02; A61B 5/24 20060101
A61B005/24 |
Claims
1. A method of calibrating a clock of an implantable
neurostimulator device, the method comprising: keeping time using a
first clock of the implantable neurostimulator device, wherein the
first clock runs continuously and is operating based upon a
reference voltage generated within a circuitry of the implantable
neurostimulator device; triggering a calibration protocol; turning
on a second clock within the implantable neurostimulator device;
calibrating the first clock based on the second clock to correct
for thermally dependent time drift; and turning off the second
clock.
2. The method of claim 1, wherein the reference voltage is
associated with an RC circuit to produce a time reference.
3. The method of claim 1, wherein an event triggers the calibration
protocol, wherein the event is a period of time determined by the
first clock.
4. The method of claim 3, wherein the period of time is few hours,
a day, a few days, a week, a couple of weeks, a month, a few
months, or a year.
5. The method of claim 1, wherein an event triggers the calibration
protocol, wherein the event is a change in the reference voltage
above a threshold value.
6. The method of claim 1, wherein the second clock comprises a
piezoelectric clock.
7. An implantable neurostimulator device comprising: a first clock
configured to keep time within the implantable neurostimulator
device; and a second clock having more accurate time-keeping
capabilities than the first clock, wherein the second clock is
configured to be in an off or idle mode while the first clocking is
running; and a control circuitry configured to be triggered by an
event such that upon triggering, the control circuitry turns the
second clock on, uses the second clock to calibrate the first
clock, and then turns the second clock off.
8. The implantable neurostimulator device of claim 7, wherein the
first clock is configured to count time based upon a reference
voltage generated by the control circuitry.
9. The implantable neurostimulator device of claim 7, wherein the
second clock comprises a piezoelectric crystal oscillator.
10. The implantable neurostimulator device of claim 7, wherein the
event comprises a preset signal programmed into the control
circuitry.
11. The implantable neurostimulator device of claim 10, wherein the
event is a temperature change.
12. The implantable neurostimulator device of claim 10, wherein the
preset signal is based on a set length of time.
13. The implantable neurostimulator device of claim 10, wherein the
preset signal is a voltage value above a certain threshold.
14. A leadless, implantable microstimulator device comprising: a
housing; at least two electrically conductive contacts disposed on
the housing; a microcontroller configured to control stimulation of
a vagus nerve from the electrically conductive contacts; a first
clock configured to keep time; and a second clock having more
accurate time-keeping capabilities than the first clock, wherein
the second clocking is configured to periodically calibrate the
first clock.
15. The leadless, implantable microstimulator device of claim 14,
wherein the second clocking module is configured to be in an idle
mode when not calibrating the first clock.
16. The leadless, implantable microstimulator device of claim 14,
further comprising: a resonator comprising a coil and a capacitor
configured to resonate at a predetermined frequency range, wherein
an electronic assembly is configured to receive power from the
resonator to charge a battery.
17. The leadless, implantable microstimulator device of claim 14,
wherein a control circuitry is configured to be triggered by an
event such that upon triggering, the control circuitry turns the
second clock on, uses the second clock to calibrate the first
clock, and then turns the second clock off.
18. The leadless, implantable microstimulator device of claim 17,
wherein the control circuitry is configured to correct a time drift
of the first clock after a calibration is performed.
19. The leadless, implantable microstimulator device of claim 17,
wherein the event comprises a preset signal programmed into the
control circuitry.
20. The leadless, implantable microstimulator device of claim 19,
wherein the preset signal is based on a set length of time, a
voltage value threshold, or a current value threshold.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This patent application is a continuation of U.S. patent
application Ser. No. 16/785,400, filed Feb. 7, 2020, titled
"SYSTEMS AND METHODS FOR ESTABLISHING A NERVE BLOCK," now U.S. Pat.
No. 11,278,718, which is a continuation of U.S. patent application
Ser. No. 15/406,619, filed Jan. 13, 2017, titled "SYSTEMS AND
METHODS FOR ESTABLISHING A NERVE BLOCK," now U.S. Pat. No.
10,596,367, which claims the benefit under 35 U.S.C. .sctn. 119 of
U.S. Provisional Patent Application No. 62/278,337, filed Jan. 13,
2016, titled "SYSTEMS AND METHODS FOR ESTABLISHING A NERVE BLOCK"
and U.S. Provisional Patent Application No. 62/286,952, filed Jan.
25, 2016, titled "CALIBRATION OF CLOCK SIGNAL WITHIN AN IMPLANTABLE
MICROSTIMULATOR," each of which is herein incorporated by reference
in its entirety.
[0002] This patent application may be related to U.S. patent
application Ser. No. 14/931,711, titled "NERVE CUFF WITH POCKET FOR
LEADLESS STIMULATOR," filed on Nov. 3, 2015, Publication No.
US-2016-0051813-A1, which claims priority as a continuation of U.S.
patent application Ser. No. 14/536,461, titled "NERVE CUFF WITH
POCKET FOR LEADLESS STIMULATOR," filed on Nov. 7, 2014, now U.S.
Pat. No. 9,174,041, which is a divisional of U.S. patent
application Ser. No. 12/797,452, titled "NERVE CUFF WITH POCKET FOR
LEADLESS STIMULATOR", filed on Jun. 9, 2010, now U.S. Pat. No.
8,886,339, which claims the benefit under 35 U.S.C. .sctn. 119 of
U.S. Provisional Patent Application No. 61/185,494, titled "NERVE
CUFF WITH POCKET FOR LEADLESS STIMULATOR", filed on Jun. 9, 2009,
each of which is herein incorporated by reference in its
entirety.
INCORPORATION BY REFERENCE
[0003] All publications and patent applications mentioned in this
specification are herein incorporated by reference in their
entirety to the same extent as if each individual publication or
patent application was specifically and individually indicated to
be incorporated by reference.
FIELD
[0004] Embodiments of the invention relate generally to systems,
devices, and methods of establishing a nerve block, and more
specifically to systems, devices, and method of delivering a drug
to establish a nerve block.
BACKGROUND
[0005] A nerve block can be used to treat a variety of pain, such
as chronic pain, acute pain, or the pain resulting from a surgical
procedure. The nerve block can be established by delivering a local
anesthetic to a nerve or ganglia to block a specific nerve
distribution to reduce or eliminate pain in a specific portion of
the anatomy. The anesthetic is typically delivered to the nerve by
needle injection or catheter infusion. One drawback with this
delivery method is that the anesthetic may diffuse rapidly into the
surrounding tissue and into the vasculature, which can reduce the
effectiveness of the anesthetic at the target site and cause
adverse side effects.
[0006] An alternative technique for establishing a nerve block is
via electrical stimulation of the nerve or ganglia. However, such
electrical stimulation typically requires a relatively high level
of power in order to block the nerve, which results in a rapid
discharge of a battery powered device.
[0007] Accordingly, it would be desirable to provide a system and
method for establishing a nerve block in an efficient and effective
manner.
[0008] Furthermore, in any implanted device including circuitry it
may be useful or necessary to include some form of time keeping or
clocking function. A common example of such an implantable device
is a pacemaker which must keep time for each beat of the patient's
heart. Other examples include an implantable neuro stimulation
device that periodically outputs some form of stimuli to address
some underlying disorder (e.g. chronic pain). Nerve blocking
implants are an example of such an implantable neurostimulation
device. A clocking function may be necessary or helpful in these
implantable devices because stimulating output from these devices
may occur periodically and/or regularly over some period of time.
Thus, these devices may utilize a clocking function to keep track
of when a simulating session has occurred or will occur, and
particularly clocks that are able to determine the time of day
and/or date.
[0009] In designing the clocking function within implantable
devices, certain considerations should be addressed. While a high
level of accuracy is always desirable, there may be certain
drawbacks associated with having a clocking assembly with high
accuracy. While highly accurate main clocking systems are able to
synchronize and coordinate various circuit and component
operations, a major drawback is that they operate on a relatively
large current and thus consume a lot of power. In addition, high
accuracy clocking mechanism such as piezoelectric crystals are more
expensive and more prone to damage. Because implantable devices are
powered by batteries with a finite life and more recently through
wireless charging, it is desirable to have a clocking mechanism for
an implantable device that is able to maintain accuracy but does
not draw a lot of power and is fairly inexpensive. Thus, it would
be advantageous to have a clocking system that incorporated the low
power consumption characteristics of a less accurate clocking
module but still maintain a certain level of clocking accuracy.
SUMMARY OF THE DISCLOSURE
[0010] The present invention may relate generally to systems,
devices, and methods of establishing a nerve block, and more
specifically to systems, devices, and method of delivering a drug
to establish a nerve block.
[0011] In some embodiments, the apparatus for establishing a nerve
block may include a nerve cuff. A nerve cuff can include a cuff
body having a channel extending within the length of the cuff body
for passage of a nerve; a reservoir within the cuff body, the
reservoir configured to hold a drug, the reservoir in fluid
communication with the channel; and an elongate opening slit
extending the length of the cuff body configured to be opened to
provide access to the channel, and configured to be closed around
the channel and thereby enclose the cuff body around the nerve.
[0012] In some embodiments, the nerve cuff further includes a
controller disposed within the cuff body; and an electrode in
electrical communication with the controller, the electrode
configured to be in electrical communication with the nerve when
the nerve is enclosed in the channel.
[0013] In some embodiments, the controller and electrode are
configured to sense electrical activity in the nerve enclosed in
the channel.
[0014] In some embodiments, the nerve cuff further includes a pump,
wherein the controller is configured to activate the pump to
transfer drug from the reservoir to the channel based in part on
the sensed electrical activity of the nerve.
[0015] In some embodiments, the pump is a screw pump.
[0016] In some embodiments, the electrode is in electrical
communication with an electrical pulse generator and is configured
to deliver electrical stimulation to the nerve enclosed in the
channel.
[0017] In some embodiments, the electrode comprises a lumen in
fluid communication with the reservoir and the channel, the lumen
of the electrode configured to deliver drug from the reservoir to
the channel.
[0018] In some embodiments, the controller is programmable.
[0019] In some embodiments, the controller is programmed to drive
the pump at a constant rate.
[0020] In some embodiments, the controller is programmed to drive
the pump at an intermittent rate.
[0021] In some embodiments, the nerve cuff further includes a drug
disposed within the reservoir.
[0022] In some embodiments, the drug is disposed in a passive
diffusion matrix and both the drug and passive diffusion matrix are
disposed within the reservoir.
[0023] In some embodiments, the drug is an anesthetic or
analgesic.
[0024] In some embodiments, the nerve cuff further includes a
needle in fluid communication with the reservoir, the needle
configured to deliver drug from the reservoir to the nerve.
[0025] In some embodiments, a system for establishing a nerve block
on a nerve is provided. The system includes an implantable drug
delivery device that includes a housing; a reservoir disposed
within the housing, the reservoir configured to hold a drug; a pump
disposed within the housing, the pump configured to meter the drug
out of the reservoir; and a controller in communication with the
pump, the controller configured to control the pump. The system
further includes a sensor in communication with the controller,
wherein the controller is configured to activate the pump when the
sensor detects electrical activity from a nerve that meets or
exceeds a predetermined threshold.
[0026] In some embodiments, the sensor comprises a wireless
transmitter configured to communicate wirelessly with the
controller.
[0027] In some embodiments, the sensor is configured to be remotely
placed away from the implantable drug delivery device.
[0028] In some embodiments, the housing includes a channel
extending within the length of the housing for passage of a nerve;
and an elongate opening slit extending the length of the housing,
the elongate slit configured to be opened to provide access to the
channel, the elongate slit configured to be closed around the
channel and thereby enclose the housing around the nerve.
[0029] In some embodiments, the system further includes a
microstimulator that is removably disposed in a pocket within the
housing, wherein the elongate opening slit is configured to be
opened to provide access to the pocket, and configured to be closed
around the pocket to secure the microstimulator within the
pocket.
[0030] In some embodiments, a method of establishing a nerve block
on a nerve is provided. The method includes implanting a drug
delivery device proximate the nerve, the drug delivery device
configured to deliver a drug to the nerve; sensing an electrical
signal transmitted to or by the nerve; and delivering a drug from
the drug delivery device to the nerve based at least in part on the
step of sensing an electrical signal transmitted to or by the
nerve.
[0031] In some embodiments, the drug delivery device includes an
electrode configured to sense the electrical signal.
[0032] In some embodiments, the method further includes delivering
an electrical stimulus to the nerve through the electrode.
[0033] In some embodiments, the method further includes implanting
a remote sensor configured to sense the electrical signal.
[0034] In some embodiments, the remote sensor and the drug delivery
device are in wireless communication.
[0035] In some embodiments, the method further includes placing the
nerve within a channel that extends through the drug delivery
device, wherein the drug is delivered to the channel.
[0036] In some embodiments, the method further includes opening a
slit on the drug delivery device to provide access to the channel;
and closing the slit to secure the nerve within the channel.
[0037] In any of the apparatuses described herein, the apparatuses
described herein may be configured to include a nerve cuff and to
apply electrical stimulation to induce a nerve block.
[0038] Also described herein are apparatuses (systems and devices)
having a dual clocking system in which a generally less accurate,
but lower power, clock may run continuously and be updated
periodically with a more accurate secondary clock. Although these
apparatuses are described in the context of an apparatus configured
for use in deploying a nerve block, this principle may be
implemented in any implantable system. For example, generally
described herein are apparatuses and methods for calibrating a
first clock within an implantable device with a more accurate
secondary clock. The first (e.g., central) clock may be the primary
time keeping mechanism within the implantable device. While not all
implantable devices require a time-keeping unit, those that provide
periodic outputs to the patient often require a method for keeping
time that contribute to controlling when an output is given.
[0039] For example, described herein are implantable neuro
stimulator device having a low-power clock calibration system. Such
a device may include: a first clock configured to keep time within
the implantable neurostimulator; a second clock having more
accurate time-keeping capabilities than the first clock, wherein
the second clock is in an off or idle mode while the first clocking
is running; and control circuitry configured to be triggered by an
event such that upon triggering, the control circuitry turns on the
second clock, and uses the second clock to calibrate the the first
clock, then turns the second clock back off.
[0040] The first clock may count time based upon a reference
voltage generated within a circuitry of the implantable device. The
second clock may comprises a piezoelectric crystal oscillator. The
control circuitry may be configured to be triggered by an event
comprising a preset signal programmed into the control
circuitry.
[0041] In some variations, the event or trigger is thermal, e.g.,
temperature change.
[0042] In some variations, the preset signal may be based on a set
length of time, such as a few hours, a day, a few days, a week, a
couple of weeks, a month, or a few months. The preset signal may be
a voltage value above a certain threshold.
[0043] Also described herein are methods of calibrating a
neurostimulator. For example, a method of calibrating a clock
within an implantable neurostimulator device may include: keeping
time using a first clock of the implantable neurostimulator device,
wherein the first clock runs continuously and is operating based
upon a reference voltage generated within a circuitry of the
implantable neurostimulator device; triggering a calibration
protocol; turning on a reference clock within the implantable
neurostimulator device; and calibrating the first clock based on
the reference clock to correct for thermally-dependent time drift;
and turning off the reference clock.
[0044] The first clock may comprise a reference voltage associated
with an RC circuit to produce a time reference.
[0045] As mentioned above, the event that triggers the calibration
may be thermal or temporal. For example, the event that triggers
the calibration protocol may be a period of time (e.g., as
determined by the first clock). The length of time may be a few
hours, a day, a few days, a week, a couple of weeks, a month, a few
months, and a year.
[0046] In some variations, the event that triggers the calibration
protocol may be a change in the reference voltage above a threshold
value.
[0047] As mentioned, the second clock may comprise a piezoelectric
clock.
[0048] Also described herein are neurostimulator devices including
these self-calibrating clocks. For example, described herein are
leadless, implantable microstimulator devices for treating chronic
inflammation. Such a device may include: a housing; at least two
electrically conductive contacts disposed on the housing; a
resonator within the sealed capsule body, the resonator comprising
a coil and a capacitor configured to resonate at a predetermined
frequency range; a battery within the housing; and an electronic
assembly within the housing; wherein the electronic assembly
comprises power management circuitry configured to receive power
from the resonator to charge the battery, a microcontroller
configured to control stimulation of the vagus nerve from the
electrically conductive contacts, a first clock configured to keep
time, a second clock having more accurate time-keeping capabilities
than the first clock, wherein the second clocking is configured to
periodically calibrate the first clock.
[0049] While having a central clocking module that is able to keep
highly accurate time would be ideal, higher accuracy time-keeping
modules are not only more expensive, but also require more power.
Thus, it would be advantageous to have an internal clocking
arrangement that is able to provide sufficient clocking accuracy
for the lifetime of the implanted device but does not drain the
power from the implanted device in an inordinately quick
fashion.
[0050] Described herein are clock calibration systems contained
within an implantable device. The system includes a first clocking
module configured to keep time within the implantable device for
the majority of the time. The system also includes a second
clocking module that possesses more accurate time-keeping
capabilities that only turns on when a calibration routine is
triggered. For the remainder of the time, the second clocking
module is either in an OFF or idle mode. The triggering event may
be the passage of a certain amount of time, or by a threshold
parameter being met. In some instances, the triggering event may be
a preset signal programmed into the control circuitry. the preset
signal is based on a set length of time, such as a few hours, a
day, a few days, a week, a couple of weeks, a month, or a few
months. The preset signal may also be a voltage or current value
above a certain threshold value.
[0051] The system also includes control circuitry that is able to
coordinate signals triggered by the event and signals sent to the
central clocking module and the secondary clocking module. The
system also may include a calibration module that corrects any time
drifts within the first or central clocking module after the
clocking calibration has been performed. In some examples, the
first clocking module are able to measure and count time based upon
a reference voltage generated within general circuitry of the
implantable device. In some instances, the more accurate secondary
time keeping module is a piezoelectric crystal oscillator.
[0052] Also disclosed herein, is a method of calibrating a central
clocking module within an implantable device. The method includes
obtaining a clocking value associated with the central clocking
module, where the clocking value is associated with how the central
clocking module keeps time, establishing an event that will trigger
a calibration protocol of the clocking module using a reference
clocking module, activating the reference clocking module from an
OFF mode to an active mode, calibrating the central clocking module
based on the reference voltage, correcting any time drifts within
the central clocking module, and turning off the reference clocking
module. The clocking value is associated with a reference voltage
associated with a reference voltage associated with the clocking
module charges an RC circuit to produce a time reference. The
events that trigger the calibration step may be the running of a
set amount of time where at the end of such a period of time, a
calibration routine is run. The length of time may be a few hours,
a day, a few days, a week, a couple of weeks, a month, a few
months, and a year. The event that triggers the calibration
protocol may also be a change in the reference voltage above a
threshold value.
[0053] Also disclosed herein are implantable microstimulation
devices for treating chronic inflammation. The implantable device
may include a housing, at least two electrically conductive
contacts disposed on the housing, a resonator within the sealed
capsule body, where the resonator comprising a coil and a capacitor
configured to resonate at a predetermined frequency range, a
battery within the housing, and an electronic assembly within the
housing. The electronic assembly may include a power management
circuitry configured to receive power from the resonator to charge
the battery, a microcontroller configured to control stimulation of
the vagus nerve from the electrically conductive contacts, a first
clocking module configured to keep time, a second clocking module
having more accurate time-keeping capabilities than the first
clocking module, and where the second clocking module is configured
to periodically calibrate the first clocking module.
BRIEF DESCRIPTION OF THE DRAWINGS
[0054] FIG. 1A is a perspective view depicting a nerve cuff with an
electrical (e.g., neurostimulation device) implanted proximate a
nerve, according to an embodiment of the invention. This implant
may also be configured to include a reservoir for delivery of a
drug; alternatively or additionally, this implant may be configured
to apply high-frequency nerve-block stimulation to the nerve from
one or more electrodes (e.g., electrode pairs).
[0055] FIG. 1B is a top view depicting an implanted nerve cuff with
stimulation device of FIG. 1A.
[0056] FIG. 1C is a top view of another variation of an implanted
nerve cuff including a reservoir for delivery of a nerve blocking
agent.
[0057] FIG. 1D is a top view of another variation of an implanted
nerve cuff including a reservoir for delivery of a nerve blocking
agent, including a reservoir and one or more (one is shown) cannula
for delivery of the active agent, which may be metered.
[0058] FIG. 1E is another example of a nerve cuff apparatus adapted
for delivery of a nerve blocking agent (such as a drug) including a
connection to a remote depot for holding (and/or loading or
reloading) agent into the apparatus. Either or both the nerve cuff
and/or the implanted and tethered depot may include control
circuitry for controlling delivery of the blocking agent.
[0059] FIG. 2 is a front view depicting an implanted nerve cuff
with strain relief according to an embodiment of the invention.
[0060] FIG. 3 is a front view depicting an implanted nerve cuff
with suture holes according to an embodiment of the invention.
[0061] FIG. 4 is an open view depicting the nerve cuff with suture
holes of FIG. 3.
[0062] FIG. 5 is a top view depicting a closing device for the
implanted nerve cuff.
[0063] FIG. 6 is a perspective view depicting marsupializaton of
components such as electronic circuitry and/or a drug depot within
a pocket of the nerve cuff of FIG. 1A;
[0064] FIG. 7A is a top view depicting a nerve cuff having a
conforming shield according to an embodiment of the invention.
[0065] FIG. 7B is a front view of the nerve cuff of FIG. 7A.
[0066] FIG. 8A is a top view depicting another example of an open
nerve cuff.
[0067] FIG. 8B is a front view of the nerve cuff of FIG. 8A.
[0068] FIG. 8C is a top view depicting the nerve cuff of FIG. 8A in
a closed configuration.
[0069] FIGS. 9A and 9B show side views through a section of the
cuff body wall, indicating uniform and varying thicknesses,
respectively.
[0070] FIGS. 10A-10C illustrate one variation of a nerve cuff as
described herein. FIG. 10A shows an end view, FIG. 10B is a side
perspective view, FIG. 10C is a side view.
[0071] FIGS. 11A-11H illustrate steps for inserting a nerve cuff
such as the nerve cuffs described herein.
[0072] FIG. 12A shows an embodiment of a nerve cuff having a drug
reservoir for releasing drug to a nerve.
[0073] FIG. 12B shows another embodiment of a nerve cuff having a
drug reservoir.
[0074] FIG. 12C shows yet another embodiment of a nerve cuff having
a drug reservoir.
[0075] FIG. 13 is a flowchart showing the steps of calibrating a
first clocking module ("first clock") with a second clocking module
("second clock").
[0076] FIG. 14 is a diagram showing calibration of a first clocking
module by a second clocking module based on a change in
voltage.
[0077] FIG. 15 is a diagram showing calibration of a first clocking
module by a second clocking module based on a pre-determined period
of time.
DETAILED DESCRIPTION
[0078] Described herein are apparatuses (devices, systems,
including implants) configured to apply a nerve block. These
devices may be part of or used in conjunction with a nerve
stimulator that delivers electrical stimulation to a nerve. In some
variations, the nerve block may be part of a nerve sensing and/or
stimulation apparatus that provides electrical stimulation to
modulate the activity of the nerve and cause a wide variety of
effects. For example, electrical stimulation of the vagus nerve can
result in a reduction of inflammation through activation of the
cholinergic anti-inflammatory pathway.
[0079] Nerve blocking drugs and/or electrical stimulation can be
delivered to a nerve. For example, an anesthetic or analgesic can
be delivered to the nerve to establish a nerve block or otherwise
modulate the activity of the nerve, with or without electrical
nerve stimulation. In some embodiments, the nerve securing device
described herein can also be used to deliver drugs to the
nerve.
[0080] Referring to FIG. 1A, one example of a nerve cuff 100
adapted for holding a device coupled to a nerve 102 is shown. Nerve
102 can comprise any nerve in the human body targeted for
therapeutic treatment, such as, for example, the vagus nerve. Nerve
cuff adapter 100 generally comprises an outer carrier or cuff 104
body that can comprise any of a variety of medical grade materials,
such as, for example, Silastic.TM. brand silicone elastomers, or
Tecothane.TM. polymer.
[0081] In general, a nerve cuff including a cuff 104 body having
(or forming) one or more pouches or pockets 106 for removably
receiving an active, implantable stimulation device 108 (e.g.,
including a stimulation device configured to apply a nerve block
electrical signal) having one or more integrated, leadless
electrodes 110 on a surface of stimulation device 108 proximate
nerve 102. Alternatively or additionally, the one or more pouches
may include a depot holding an active agent and/or a controller
(including circuitry and/or a valve for regulating flow of active
agent from the depot). As illustrated in FIGS. 1A and 1B, a nerve
cuff 100 may wrap around nerve 102 such that electrodes 110 and/or
one or more outputs 133 for an active agent from the drug depot are
positioned proximate nerve 102. These outputs 133 may be regulated
by including a valve, pump, or other fluid control to regulate when
an active agent is delivered from the apparatus onto the nerve.
[0082] The depot (which may be referred to as a reservoir) may be
of any appropriate size. For example, the depot may include between
0.1 and 10 mL of liquid drug solution (e.g., between 0.1 and 5 mL,
etc.). In some variations, the depot includes a solid drug
formulation that is configured to be applied (and may include being
mixed with fluid already present or surrounding the nerve). As
mentioned, the depot may be refillable, as from an external port
and/or from a second internal depot.
[0083] Contacts or electrodes 110 can be positioned directly
against nerve 102, as illustrated in FIG. 1B, or in close proximity
to nerve.
[0084] Referring specifically to FIG. 1C, in some variations the
nerve cuff may include a pocket holding a depot 142 that includes a
drug or other active agent (such as an anesthetic or any other
compound for topically inhibiting nerve activity). Drug may be
delivered from the depot onto the nerve and kept at a locally
precise concentration for a a sustained period by holding it within
the nerve cuff surrounding the nerve 102, allowing lower amounts of
active agent to be applied more precisely over all or just a
portion of the nerve. In some variations additional depots or
reservoirs may be included for adding additional agents to the
nerve or other regions of the nerve within the cuff. In some
variations a second reservoir may include a wash-out material
(e.g., saline) for diluting or removing the drug or active agent.
In any of these variations, a controller (e.g., electronics board)
for releasing or delivering the active agent/drug may be included.
In FIG. 1A, the controller may be included instead of or along with
(e.g., integrated into) the electronics 108 of the stimulator. In
FIG. 1D, for example, the depot holding the active agent/drug 142'
may be connected to the output 133 onto the nerve in the cuff by a
channel 145; this channel may be regulated (opened/closed) by a
drug delivery controller 147 that may include hardware, software
and/or firmware for actively controlling the application of drug
onto the nerve. The drug delivery controller may also include a
valve for opening/closing the channel, such as a piezo valve, or a
pump. The depot 142 may be pressurized so that drug is emitted when
the channel 145 is opened by the drug delivery controller 147. The
controller may also regulate pressurizing of the depot.
[0085] In some variations, the depot may be located remotely from
the nerve cuff, as illustrated in FIG. 1E. In this example, the
nerve cuff 100 is configured to include one or more outputs for
active agent/drug (not visible in FIG. 1E), and may also include a
drug delivery controller for regulating the delivery of drug onto
the nerve. A second depot may be included within the cuff, which
may be filled by the primary depot 142'. The remote depot 142' may
be connected by tubing 148
[0086] In general, a drug delivery controller may include control
logic for controlling delivery of the active agent onto the nerve.
The drug delivery controller may therefore include a timer (e.g.,
for delivering doses at a prescribed time) and/or may include
wireless communication circuitry and/or antenna for transmitting
and/or receiving control information from a remote source. The drug
delivery controller may also include a power source/supply (e.g.,
battery and/or inductive loop(s), capacitive power source, etc.),
and one or more pumps and/or valves. In particular, a micro pump
for delivering small (e.g., less than a 1 ml, less than 0.5 ml,
less than 0.1 ml, etc.) of drug per time period (e.g., min, second,
etc.). Any of the apparatuses described herein may be configured to
apply drug based on activity on the nerve. For example the drug
delivery controller may include input from one or more electrodes
(or may be integrated with an electrical activity detector)
receiving input from the electrodes on the nerve within the cuff or
separate from the cuff. Electrical activity above a particular
threshold may trigger release of drug.
[0087] In one embodiment, a pocket 106 for containing a drug
delivery controller, stimulation device, and/or drug depot. One or
more pockets may be defined by the open space between the nerve 102
and the inner surface of the cuff body 104. The sensing and/or
stimulation device, drug depot and/or drug delivery controller
(including any pump and/or valve components) can be passively
retained within pocket by the cuff body, or can be actively
retained on cuff body with fastening means, such as, for example,
sutures. In other embodiments, a pocket can comprise a pouch-like
structure attached to cuff body into which sensing and/or
stimulation device, drug depot and/or drug delivery controller can
be inserted. The sensing and/or stimulation device, drug depot
and/or drug delivery controller can be passively retained within a
pouch-like pocket by simply inserting into the pocket or can be
actively retained with fastening means. A pouch-like pocket can be
positioned either in the interior or on the exterior of cuff body
104. Pouch-like pocket and/or cuff body can include access openings
to allow electrodes and/or drug outputs (including needles or
cannula) to be positioned directly proximate or adjacent to nerve
102.
[0088] Cuff body 104 can have a constant thickness or a varying
thickness as depicted in FIGS. 9A and 9B. The thickness of cuff
body 104 can be determined to reduce the palpable profile of the
device once the stimulation device is inserted. In one embodiment,
the thickness of cuff body can range from about 1 to about 30 mils,
or from about 5 to about 20 mils. In one embodiment shown in FIG.
9B, cuff 104 can have a greater thickness at a top and bottom
portion of the cuff and a smaller thickness in a middle portion
where the stimulation device is contained.
[0089] A key obstacle to overcome with implanting stimulation
devices proximate nerves or nerve bundles is attaching a rigid
structure that makes up the stimulation device along a fragile
nerve in soft tissue. In one embodiment of the invention, this
issue is resolved by encasing nerve 102 and device 108 in a cuff
body 104 that comprises a low durometer material (e.g.,
Silastic.TM. or Tecothane.TM.) as described above, that conforms
around nerve 102. Further, as illustrated in FIG. 2, cuff body 104
can comprise strain reliefs 114 on its ends that reduce or prevent
extreme torsional rotation and keep nerve 102 from kinking. Strain
reliefs 114 can coil around nerve 102, and are trimmable to a
desired size, such as the size of nerve 102. Further, strain relief
114 can be tapered. In some variations, the lateral ends of the
nerve cuff, forming the channel into which the nerve may be place,
are tapered and have a tapering thickness, providing some amount of
support for the nerve. In some variations, the channel through the
nerve cuff in which the nerve may sit, is reinforced to prevent or
limit axial loading (e.g., crushing) of the nerve or associated
vascular structures when the nerve is within the cuff.
[0090] Given the design or architecture of cuff body 104, any
vertical movement of cuff body 104 on nerve 102 is not critical to
electrical performance, but can result in friction between device
108 and nerve 102 that could potentially damage nerve 102. For that
reason, device 108 should readily move up and down nerve 102
without significant friction while being sufficiently fixated to
nerve 102 so that eventually connective tissue can form and aid in
holding device 108 in place. The challenge is stabilizing device
108 so that it can be further biologically stabilized by connective
tissue within several weeks.
[0091] Nerve cuff 100 should not be stabilized to surrounding
muscle or fascia that will shift relative to the nerve. Therefore,
referring to FIGS. 3 and 4, nerve cuff 100 can further comprise
connection devices, such as suture holes or suture tabs, for
coupling and stabilizing cuff body 104 with device 108 to at least
one of the nerve bundle or nerve 102, and the surrounding sheath
that contains nerve 102. In one embodiment of the invention, for
example, as shown in FIG. 3, cuff body 104 can comprise suture
holes 116 that can be used with sutures to couple cuff 104 body
with device 108 to the surrounding nerve sheath. In an alternative
embodiment of the invention, shown in FIG. 4, suture tabs 118 with
suture holes 116 extend from one or both sides of cuff body
104.
[0092] Several stabilizing mechanisms can be used, including suture
tabs and holes, staples, ties, surgical adhesives, bands, hook and
loop fasteners, and any of a variety of coupling mechanisms. FIGS.
3 and 4, for example, illustrates suture tabs and holes that can be
fixed to the surrounding sheath with either absorbable sutures for
soft tissue or sutures demanding rigid fixation.
[0093] FIG. 5 illustrates sutures 120 that clamp or secure cuff
body 104 with device 108 to a surgeon-elected tension. Sutures 120
can be tightened or loosened depending on the level of desired
stability and anatomical concerns. As shown in FIG. 5, a gap 122
can be present so long as cuff adapter 100 is sufficiently secured
to nerve 102, with a limit set to a nerve diameter to prevent
compression of the vasculature within nerve 102. Surgical adhesives
(not shown) can be used in combination with sutures 120 on
surrounding tissues that move in unison with the neural tissue.
[0094] Muscle movement against cuff adapter 100 can also transfer
undesired stresses on nerve 102. Therefore, in an embodiment of the
invention, low friction surfaces and/or hydrophilic coatings can be
incorporated on one or more surfaces of cuff body 104 to provide
further mechanisms reducing or preventing adjacent tissues from
upsetting the stability of nerve cuff 100.
[0095] FIG. 6 illustrates a nerve cuff 100 with a sensing and/or
stimulation device, drug depot and/or drug delivery controller
device removably or marsupially secured within pocket or pouch 106
of cuff body 104. By the use of recloseable pouch 106, active
stimulator device 108 can be removed or replaced from cuff body 104
without threatening or endangering the surrounding anatomical
structures and tissues. Device 108 can be secured within cuff body
104 by any of a variety of securing devices 124, such as, for
example, sutures, staples, ties, zippers, hook and loop fasteners,
snaps, buttons, and combinations thereof. Sutures 124 are shown in
FIG. 6. Releasing sutures 124 allows access to pouch 106 for
removal or replacement of device 108. Not unlike typical cuff style
leads, a capsule of connective tissue can naturally encapsulate
nerve cuff 100 over time. Therefore, it will most likely be
necessary to palpate device 108 to locate device 108 and cut
through the connective tissue capsule to access sutures 124 and
device. The removable/replaceable feature of nerve cuff 100 is
advantageous over other cuff style leads because such leads cannot
be removed due to entanglement with the target nerve and critical
vasculature.
[0096] As discussed above, compression of nerve 102 must be
carefully controlled. Excess compression on nerve 102 can lead to
devascularization and resulting death of the neural tissue.
Compression can be controlled by over-sizing or rightsizing nerve
cuff 100, so that when pocket sutures 124 are maximally tightened,
the nerve diameter is not reduced less that the measured diameter.
Cuffs formed from Silastic.TM. or Tecothane.TM. materials are
relatively low cost, and therefore several sizes can be provided to
the surgeon performing the implantation of nerve cuff 100 to better
avoid nerve compression.
[0097] Sensing and/or stimulation devices, drug depots and/or drug
delivery controllers, may be large enough to be felt and palpated
by patients. Referring to FIG. 7A, to avoid such palpation, nerve
cuff 100 can further comprise a protecting shield 126 conforming to
the shape of the anatomical structures, such as in the carotid
sheath. In this embodiment, nerve cuff 100 is secured around the
vagus nerve, while isolating device 108 from contact with both the
internal jugular vein (IJV) 132, and common carotid artery 134.
Shield 126 then further isolates device 108 from other surrounding
tissues. The profile of the entire cuff adapter 100 may be
minimized while maintaining the compliance of such materials as
Silastic.TM. or Tecothane.TM.. In one embodiment of the invention,
protective shield 126 is formed from a PET material, such as
Dacron.RTM., optionally coated with Silastic.TM. or Tecothane.TM.
forming a thin and compliant structure that will allow for tissue
separation when required.
[0098] When a nerve does not provide sufficient structural strength
to support nerve cuff adapter 100, collateral structures can be
included in or on cuff body 104. Because of a high degree of
anatomical variance such a scheme must demand the skill of the
surgeon to utilize a highly customizable solution. FIG. 8A
illustrates a variable size nerve cuff 100 with a wrappable
retainer portion 128 extending from cuff body 104. As shown in FIG.
8C, cuff body 104 is secured around nerve 102, while retainer
portion 128 is secured around the sheath or other surrounding
anatomical structures, such as the IJV 132 and/or carotid artery
134. As shown in FIG. 8B, wrappable retainer portion 128 can
include securing devices 130, such as suture holes, for securing
the entire nerve cuff 100 around the desired anatomical structures.
This configuration allows for access to sensing and/or stimulation
device, drug depot and/or drug delivery controller devices 108
through pocket 106 as in previous embodiments, while adapting to a
multitude of anatomical variations to obtain the desired stability
of nerve cuff 100 on nerve 102.
[0099] FIGS. 10A-10C illustrate a variation of a nerve cuff that
includes a cuff body forming a channel (into which a nerve may be
fitted) and an slit formed along the length of the nerve cuff body.
In this example, the nerve cuff body also includes one or more
pocket regions (not visible in FIGS. 10A-10C) within the cuff body
positioned above the nerve channel. The top of the body (opposite
from the nerve channel) includes a long slit 1003 along its length
forming on opening. The cuff body may be along the slit by pulling
apart the edges, which may form one or more flaps. In the example
shown in FIG. 10A, the slit may be split open to expose the inside
of the nerve cuff and allow the nerve to be positioned within the
internal channel, so that the cuff is positioned around the nerve.
The same split may be used to insert the sensing and/or stimulation
device, drug depot and/or drug delivery controller device as well.
In some variations a separate opening (slit or flap) may be used to
access the pocket or pouch for the sensing and/or stimulation
device, drug depot and/or drug delivery controller.
[0100] FIG. 10B shows a perspective view of the nerve cuff holding
a sensing and/or stimulation device, drug depot and/or drug
delivery controller after it has been inserted onto a nerve (e.g.,
the vagus nerve). FIG. 10C shows a side view of the same.
[0101] The exemplary cuff shown in FIGS. 10A-10C has a conformal
configuration, in which the wall thickness is relatively constant;
in some variations of a nerve cuff, the wall thickness may vary
along the perimeter. This non-uniform thickness may effectively
cushion the device relative to the surrounding tissue, even as the
patient moves or palpitates the region. This may have the added
benefit of preventing impingement of the nerve. Similarly, the
variable thickness may enable smooth transitions and help conform
the cuff to the surrounding anatomy.
[0102] The nerve cuff may be substantially rounded or conforming,
and have non-traumatic (or atraumatic) outer surfaces. As
mentioned, this relatively smooth outer surface may enhance comfort
and limit encapsulation of the nerve cuff within the tissue.
[0103] A nerve may sit within a supported channel through the nerve
cuff. The channel may be formed having generally smooth sides, so
as to prevent damage to the nerve and associated tissues. In some
variations the nerve channel though the cuff is reinforced to
prevent the cuff from pinching the device or from over-tightening
the device when closed over the nerve. Supports may be formed of a
different material forming the nerve cuff body, or from thickened
regions of the same material. Although multiple sizes of nerve cuff
may be used (e.g., small, medium, large), in some variations, an
oversized nerve cuff may be used, because the insulated cuff body
will prevent leak of current from the sensing and/or stimulation
device, drug depot and/or drug delivery controller to surrounding
tissues.
[0104] In operation, any of the devices described herein may be
positioned around the nerve, and the sensing and/or stimulation
device, drug depot and/or drug delivery controller inserted into
the nerve cuff, in any appropriate manner. FIGS. 11A-11H illustrate
one variation of a method for applying the nerve cuff around the
nerve and inserting a sensing and/or stimulation device, drug depot
and/or drug delivery controller. In this example, the patient is
prepared for application of the nerve cuff around the nerve to hold
a sensing and/or stimulation device, drug depot and/or drug
delivery controller device securely relative to the nerve (FIG.
11A). An incision is then made in the skin (.apprxeq.3 cm), e.g.,
when inserting onto the vagus nerve, along Lange's crease between
the Facial Vein and the Omohyoid muscle (FIG. 11B), and the
Sternocleidomastoid is retracted away to gain access to the carotid
sheath (FIG. 11C). The IJV is then reflected and .ltoreq.2 cm of
the vagus is dissected from the carotid wall.
[0105] In some variations, a sizing tool may be used to measure the
vagus (e.g., diameter) to select an appropriate sensing and/or
stimulation device, drug depot and/or drug delivery controller and
cuff (e.g., small, medium, large). In some variations of the
method, as described above, an oversized cuff may be used. The
nerve cuff is then placed under the nerve with the opening into the
nerve cuff facing the surgeon (FIG. 11D), allowing access to the
nerve and the pocket for holding the sensing and/or stimulation
device, drug depot and/or drug delivery controller. The sensing
and/or stimulation device, drug depot and/or drug delivery
controller can then be inserted inside cuff (FIG. 11E) while
assuring that the sensing and/or stimulation device, drug depot
and/or drug delivery controller contacts capture the nerve, or
communicate with any internal contacts/leads. The nerve cuff may
then be sutured shut (FIG. 11F). In some variations, the sensing
and/or stimulation device, drug depot and/or drug delivery
controller may then be tested (FIG. 11G) to confirm that the device
is working and coupled to the nerve. For example, a surgical tester
device, covered in a sterile plastic cover, may be used to activate
the sensing and/or stimulation device, drug depot and/or drug
delivery controller and perform system integrity and impedance
checks, and shut the sensing and/or stimulation device, drug depot
and/or drug delivery controller off. If necessary the procedure may
be repeated to correctly position and connect the sensing and/or
stimulation device, drug depot and/or drug delivery controller.
Once this is completed and verified, the incision may be closed
(FIG. 11H).
[0106] Systems for electrically stimulating one or more nerves to
treat chronic inflammation may include an implantable, wireless
sensing and/or stimulation device, drug depot and/or drug delivery
controller such as those described herein and an external charging
device (which may be referred to as a charging wand, charger, or
energizer). In some variations the system also includes a
controller such as a "prescription pad" that helps control and
regulate the dose delivered by the system. The sensing and/or
stimulation device, drug depot and/or drug delivery controller may
be secured in position using a securing device (which may be
referred to as a "POD") to hold the sensing and/or stimulation
device, drug depot and/or drug delivery controller in position
around or adjacent to a nerve.
[0107] In any of the apparatuses described herein, doses of active
agent (e.g., nerve block agent) may be applied continuously,
periodically or may the apparatus may be configured to apply a dose
or additional dose upon triggering of an event such as an
electrical activity on the never. For example, a microliter and
even picoliter doses of active agent may be delivered either
continuously or periodically (e.g., at a frequency of x uL or pL
per second, where x is between 0.001 and 10) or for a single dose
(e.g. of x uL or pL, where x is between 0.001 and 10). A single
dose may be delivered within the cuff, or multiple doses maybe
delivered within the cuff. Doses may be separated by a dosage
interval that may be predefined, regular, scheduled (based on time
of day) and/or triggered (e.g., by nerve activity). Doses may be
delivered on demand. For example, a doctor or patient may
communicate wirelessly or via an input in the drug delivery control
to trigger release of a dose.
[0108] As described above, and as shown in FIG. 12A, the nerve cuff
2800 can be modified to include a reservoir 2802 to hold an active
agent/drug, such as an anesthetic like lidocaine. The nerve cuff
2800 can have one or more outputs/channels (ports 2804) for
releasing the drug into the region surrounding the nerve 2806
within the cuff. Because the nerve cuff 2800 surrounds the portion
of the nerve 2806 where the drug is being delivered, the diffusion
of the drug away from the nerve is greatly reduced as compared to
injection or infusion of the drug using a needle or catheter.
Consequently, a low volume, low diffusion system for delivering the
drug to the nerve can be sufficient to establish an effective nerve
block over a long period of time, such as days, weeks, or months.
In some embodiments, the modified nerve cuff 2800 can be used with
a microstimulator 2808 as described herein. In other embodiments,
the modified nerve cuff can be used without a microstimulator to
deliver drug to a nerve.
[0109] In some embodiments, as shown in FIG. 12A, the nerve cuff
2800 can have a refilling port 2810 in fluid communication with the
reservoir 2802. The refilling port 2810 can be used to refill the
reservoir 2802 with drug (e.g., anesthetic). In some embodiments as
shown in FIG. 12A, the refilling port 2810 can be located on the
outer surface of the nerve cuff 2800, and a needle or catheter can
be used to access the refilling port and deliver drug to the
reservoir (depot) while the nerve blocking device remains within
the body around the nerve 2806. In some embodiments as shown in
FIG. 12B, the refilling port 2810 can be in fluid communication
with a subcutaneous or subdermal access port 2812, and a needle or
catheter can be used to access the access port 2812 and deliver
drug to the reservoir. For example, the access port 2812 can be
located at a subcutaneous location, and tubing 2814 can connect the
access port 2812 with the drug refilling port 2810 on the nerve
cuff 2800.
[0110] In some embodiments as shown in FIG. 12C, one or more of the
electrodes 2816 can be modified to include a lumen 2818 or channel
for drug delivery. For example, the modified electrode 2816 can be
a cuff type electrode, or a penetrating type electrode such as a
needle electrode, or a combination of both. The modified electrode
2816 can deliver the drug from the reservoir to the nerve 2806 in a
perifascicular or intrafascilular manner. Perifascicular delivery
means delivery of the drug around a nerve or nerve bundle, while
intrafascilular delivery means delivery of the drug into or inside
the nerve or nerve bundle. In some embodiments, a modified cuff
electrode 2816 can be used for perifascicular drug delivery, while
a modified penetrating electrode can be used for intrafascilular
drug delivery. In other embodiments, the device can have a
dedicated drug delivery lumen or needle that is separate from the
electrode.
[0111] In some embodiments, the drug can be delivered from the
reservoir using a passive diffusion matrix drug delivery system.
For example, the drug can be incorporated into a polymer matrix and
can diffuse out of the matrix and/or be release as the matrix
erodes.
[0112] In other embodiments as shown in FIGS. 12A and 12B, the drug
delivery system can use a pump 2820, such as a screw pump or other
small pump. The pump 2820 can deliver drug in a liquid form, a
solid form such as a power, or a mixed form such as a paste or
slurry, from the reservoir 2802 to the nerve 2806.
[0113] In some embodiments, the modified electrodes can be
electrically active and can be capable of delivering and/or
detecting an electrical stimulus or signal to the nerve or other
tissue. In other embodiments, the modified electrodes can be
electrically inactive, and may only be used for drug delivery.
[0114] In some embodiments, a controller can be used to control the
pump along with controlling the stimulation delivered by the
electrodes and/or the signal detection and processing by the
electrodes. The controller may be programmable and may drive the
pump to deliver drug at a constant or intermittent rate. In some
embodiments, the controller may enable manual drug dosing, where
the user can communicate with the controller using wireless
communications. In some embodiments, the controller may be
programmed and/or communicate with a computing device, such as a
tablet, smart phone, laptop, or desktop computer, using a wireless
communication protocol, such as Bluetooth or WiFi.
[0115] In some embodiments, the controller provides closed loop
control of the drug delivery. In some embodiments, the controller
can adjust the dosage of drug, i.e. the amount and/or the rate of
drug delivered, based on feedback received from a sensor. The
sensor can be the electrode described above used for local
detection of action potential activity in a nerve. Alternatively or
additionally, the sensor can be a remotely located sensor that
detects a physiological aspect of the patient, such as inflammation
or pain. For example, one or more remote sensors can be placed at a
different nerve that is remotely located from the nerve cuff but is
part of the same sensory pathway. This allows the nerve cuff with
drug delivery capabilities to be placed at an upstream, more
central location that can potentially block pain signals from
multiple nerves. Alternatively, this allows the sensors to be
placed at upstream locations to improve detection of pain signals
transmitted by the nerves while the drug delivery device is placed
at one or more downstream locations to minimize or reduce the area
affected by the drug. These remotely located sensors may
communicate wirelessly with the controller in the nerve cuff, or
the remote sensors may be directly connected to the nerve cuff
using a wire. Local detection or remote detection of action
potential activity in the any of the nerves in the pathway can
trigger the delivery of drug from the reservoir.
[0116] In some embodiments, the sensor can measure electrical
activity from the heart and can be used to measure an ECG signal.
The controller can be used to process and analyze the ECG signal to
determine heart rate and heart rate variability. In some
embodiments, the drug dosage can be modified based on the heart
rate and/or heart rate variability.
[0117] In some embodiments, the drug can be an anesthetic or
analgesic or another type of painkiller One or more drugs can be
used to provide a customizable dosing schedule tailored to the
needs of the patient. The one or more drugs can be selected based
in part on the desired wash out speed, volumetric optimization, and
drug stability. The nerve cuff can include one or more reservoirs
so that each drug can be contained in a separate reservoir, or the
drugs can be mixed together and be placed into a single reservoir.
Examples of drugs include ester based anesthetics such as procaine
(novocaine), benzocaine, chloroprocaine cocaine, cyclomethycaine,
dimethocaine, piperocaine, propoxycaine, proparacaine, and
tetracaine; and amine based anesthetics such as lidocaine,
bupivacaine (Marcaine), ropivacaine, cinchocaine, etidocaine,
levobupivacaine, mepivacaine, articaine, prilocaine, and
trimecaine.
[0118] In some embodiments, the drugs can be neurotrophic drugs
with an effect on nerves.
[0119] Since the drugs may have different time constants, the
pharmacokinetic profile of the drug or drug combination can be
tailored to match the symptoms experienced by the patient, such as
short term pain, chronic pain, or inflammation. For example,
lidocaine has a time constant of about 1 hour and Marcaine has a
time constant of about 4 hrs. Therefore, to treat inflammation or
pain lasting greater than 2 hours, it may be desirable to include
Marcaine, which persists longer than lidocaine. In contrast, to
treat inflammation or pain of shorter durations, for example, less
than 2 hours, it may be desirable to include lidocaine. In some
embodiments, both a mixture of drugs having short and long time
constants can be used. In addition, the device can be programmed to
deliver drug at regular intervals, which can be determined based on
the drug time constants and the degree of vascular profusion in the
area, and/or in an on-demand fashion. In addition, as described
above, the delivery of the drug can also be modified based on data
received from a sensor, or in an on-demand fashion.
[0120] In some embodiments, the modified nerve cuff and electrode
can be secured around the vagus nerve and both electrical
stimulation and drug(s) can be delivered to the vagus nerve. For
example, when using the nerve cuffs described herein, the slit on
the nerve cuff can be opened to allow access to a channel for
receiving the nerve. The nerve can be placed within the channel,
and the slit can then be closed to secure the nerve within the
channel of the nerve cuff.
[0121] In some embodiments, the nerve cuff and electrode can be
secured in a similar manner around a nerve responsible for
generating the sensation of pain in the patient. For example, to
establish a nerve block in the upper extremities, one or more nerve
cuffs and electrodes can be placed around or adjacent the
interscalene nerve, supraclavicular nerve, infraclavicular nerve,
and/or axillary nerve. An interscalene nerve block can be
established for surgeries to the shoulder, clavicle, or upper arm;
a supraclavicular nerve block can be established for surgeries to
the upper arm to the hand; an infraclavicular nerve block can be
established for surgeries to the elbow to the hand; and an axillary
block can be established for surgeries to the elbow to the hand. To
establish a nerve block in the chest and abdomen, one or more nerve
cuffs and electrodes can be placed around or adjacent to the
vertebral body in the paravertebral space and/or around or adjacent
to nerves in the space between the internal oblique and the
transversus abdominis muscles. To establish a nerve block in the
lower extremities, one or more nerve cuffs and electrodes can be
placed around or adjacent the lumbar plexus, the femoral nerve,
and/or the sciatic nerve.
[0122] The sensors can be positioned at or around the nerves listed
above, and on other nerves or neural structures which receive
signals from these nerves or are formed in part from these nerves,
such as the brachial plexus and lumbar plexus, or on nerves that
transmit signals to these nerves. For example, as described herein,
the nerve cuff can include an electrode for sensing electrical
signals, such as action potentials, to measure nerve activity of
the nerve attached to the nerve cuff. Alternatively or
additionally, as described above, remote sensors can be placed away
from the nerve cuff at remote locations to sense electrical
activity in nerves or nerve locations described herein. In some
embodiments, the remote locations may be closer to the source of
pain, such as near or at the extremities and joints.
[0123] In addition or alternative to the use of drug agents as
described above, any of these apparatuses may be configured to
provide an electrical nerve block using a microstimulator held
within the cuff. Electrical nerve bock may involve reversibly
blocking peripheral nerves by applying high frequency alternating
current directly on a nerve trunk. For example, a current ranging
from 5 kHz to 50 kHz may be applied (high frequency, compared to a
current of less than 1 kHz for low frequency). Efficacy of the high
frequency alternating current therapy in acute non-human animal
experiments (frog, cat) has been reported, e.g., U.S. Pat. Nos.
7,389,145 and 8,060,208 describe this electrical stimulation.
[0124] Reversibly blocking an action potential in a peripheral
nerve having a diameter exceeding 3 mm and up to about 12 mm, e.g.,
a sciatic nerve, a tibial nerve, etc., may be applied by a
neurostimulator held within any of the cuffs described herein,
providing an electrical waveform for an interval of time sufficient
to effect substantially immediate pain relief, defined generally as
within about 10 min. One embodiment uses a waveform ranging from 5
kHz to 50 kHz. One embodiment uses a 10 kHz sinusoidal waveform at
a current ranging from 4 mA to 26 mA. The electrode can be retained
in the cuff encircling the desired peripheral nerve in which the
action potential is to be blocked. The time interval may be about
10 minutes, but an interval may be selected by a magnitude
sufficient to effect pain relief in the patient. In one embodiment,
the electrical waveform to effect pain relief ranges from a voltage
from 4 V to 20 V, or a current ranging from 4 mA to 26 mA. The time
of increasing magnitude can range from about 10 seconds to about 60
seconds with a steady ramp up of voltage or current. The waveform
may be provided by a waveform generator that is part of the
apparatus. As mentioned above, the application of the nerve block
(including electrical nerve block) may be triggered by activity on
the nerve to which the cuff is attached.
Dual Clocking Apparatuses
[0125] As mentioned above, also described herein are methods and
apparatuses for keeping highly accurate time in a implant
(including, but not limited to the nerve block apparatuses
described above) using very low power. In particular, described
herein are methods and apparatuses for calibration of a first
(e.g., low power) clock/clocking mechanism, where the calibration
occurs periodically or based upon some event or signal being
detected and through use of a second, more accurate clock/clocking
mechanism.
[0126] In implantable devices, and many other electrical devices in
general, there is great demand for having systems with lower power
consumption as well as lower cost. Lower power expenditure may be
achieved through having a process that does not draw as much power,
but often this is at the expense of having less accurate outputs.
In the case with a clocking system, the use of a less accurate
clock signal may lead to lower power consumption compared to a more
accurate clocking mechanism, but a less accurate clock having lower
power consumption may result in providing output at imprecise or
unpredictable times.
[0127] One way to compensate for having a systems clocking
mechanism that is a less accurate clocking mechanism that will be
periodically calibrated with a more accurate clocking system,
including one which is present on/in the implant, but which may be
deactivated or inactive until triggered. For example, disclosed
herein is a first or central clocking mechanism that uses a
semiconductor junction to generate a reference voltage that in turn
charges an RC circuit to produce a time reference. Because these
voltage references have significant variations due to integrated
circuit characteristics and parameters and temperature, they tend
to be less accurate, though they may require lower power. Other,
typically lower power and/or lower cost clocks may be used as the
primary clock.
[0128] To compensate for the lack in accuracy of the first clocking
mechanism, a second more accurate clocking mechanism is employed.
The second, more accurate clocking mechanism may be used to
periodically recalibrate the first clocking mechanism.
[0129] More accurate clocking mechanism include real time clocks.
Real time clocks are a type of computer clock in the form of
integrated circuits. Most real time clocks use a piezoelectric
crystal oscillator, where the oscillator frequency is 32.768 kHz,
the same frequency as in quartz clocks and watches.
[0130] In one non-limiting example, a time reference clocking
module error in the RC circuit may be measured over fixed intervals
or based on a change in a pre-determined parameter (e.g. voltage or
current). Deviations may be measured against a more accurate real
time crystal oscillator clocking mechanism. Based on the measured
deviation and time elapsed since the last calibration, the amount
of time deviation in the time reference clocking module may be
calculated and corrected. Correction of any time deviation may be
occur through correcting the central clocking module.
Alternatively, the central clocking module may be temporarily
replaced with the more accurate real time crystal oscillator
clocking mechanism to bring the central clocking module back to a
correct value.
[0131] In another non-limiting example, the implantable device will
run the central clocking mechanism continuously while a second,
more accurate clocking mechanism remains in an OFF or standby mode.
Upon the occurrence of a pre-determine event or time interval, the
second, more accurate clocking mechanism may enter an active mode
and re-calibrate the central clocking mechanism. Upon completion of
the calibration routine, the second, more accurate clocking
mechanism will again revert to an OFF or standby mode until the
next calibration is triggered.
[0132] FIG. 13 shows a flowchart for visualizing the steps of
implementing a clocking calibration routine 1300. Presumably the
clocking system for the implantable device, such as a
neurostimulator, will be activated once the device is implanted in
the patient. At 1302, the systems clocking mechanism is running. At
this point, the second, more accurate clocking mechanism is in a
sleep or OFF mode (1308). At some point in time later, an even
triggers a signal being sent to the second clocking mechanism
(1304). The trigger may correspond to the beginning of a new cycle
in the implantable device. In the case of an implantable
neurostimulator, the trigger may be associated with the beginning
of a stimulation session or a combination of features of the
stimulation session (e.g. a time interval after the start of the
stimulation session). A trigger for calibration may also be a
circuit parameter that has exceeded or dropped below a threshold
value. Once the trigger event has occurred (1304), a signal is sent
to the second clocking module to turn from the OFF or standby mode
to an active mode (1312). With the second clocking module in an
active state, it will initiate the calibration routine (1310). Once
the calibration routine (1310) has been performed, any deviation
determined from running the calibration routine (1310) may be
corrected in the following step (1314). Once the deviation has been
corrected, a second signal may be sent to the second clocking
module to return to an OFF or standby mode. In the final step, a
third signal may be sent to the central clocking module to switch
it from an OFF or standby mode to an active mode. These steps may
be repeated based on a condition being satisfied, an event
occurring, or a pre-determined period of time. Also, it may be
possible to delay calibration to sometime past the triggering
event.
[0133] Turning to FIG. 14, a sample calibration routine based on
some feature or characteristic of the implanted device output is
shown. In the case of an implantable neurostimulation device,
calibration of the central clocking system may be tied to when a
stimulation session begins. In this scenario, a sensor may be
incorporated to sense when a current or voltage has increased above
a certain value and that a calibration routine should be initiated
immediately or after a set amount of time. To better visualize each
component status, FIG. 14 shows stacked signals in order from top
to bottom: a series of neurostimulation outputs for a
neurostimulator 1430, the functional state of the first or central
clocking module 1440, and the functional state of the second
clocking module 1450 that is able to perform the calibration
routine. The horizontal axis from left to right indicates the
passage of time and may be in units of minutes, hours, days, weeks,
months, and so forth.
[0134] As the diagram arbitrarily shows a snapshot of the output of
an implanted device. Initially, when the neurostimulation device is
in an idle state (1431), the central clocking module 1440 is in an
active mode 1441 and the second clocking module 1450 is in an OFF
or standby mode (1451). The central clocking module 1440 will then
continue to run for some period 1442 until a neurostimulation
session begins (1432), at that point, signals are set to the both
the central clocking module 1440 and the second clocking module
1450 when the neurostimulation output surpasses a certain threshold
value. Upon reaching this state, the central clocking module will
drop to an idle or OFF state 1442 while the second clocking module
1450 will switch from its OFF or standby mode 1451 to an active
mode 1452, where it will run a calibration routine 1453 either
immediately or at a preset time in the future. Upon completion of
the calibration routine 1453, a signal is sent to the central
clocking module to coordinate switching it from the standby mode
1442 back to an active mode 1441 and for the second clocking module
to return from an active mode 1452 to an OFF or standby mode 1451
in a coordinated fashion. These steps will repeat based on some
feature of the stimulating output from the implanted device. In
some other variations, the calibration routine may be tied to some
other feature of the stimulating output and not necessarily
correspond to the beginning of the stimulation output.
[0135] FIG. 15 shows an alternative initiation of calibration
routines in a system where a secondary, more accurate clocking
module is used to calibrate and correct any deviations experienced
by a less accurate central clocking module. In this arrangement,
the implanted device output will provide output periodically, where
the time periods may be the same or different and may be set by the
doctor or other user. A calibration routine may occur that aligns
with a given time period t, that repeats. As the diagram shows,
during the evolution of time period t, the central clocking module
is in an active state 1541, while the second clocking module is in
an OFF or inactive state 1551. At the end of the time period t, the
central clocking module will switch to an idle or OFF mode 1542
while the second clocking module will turn to an active mode 1552
to calibrate the less accurate central clocking module 1540 and
adjust for any deviations that is measured. Upon completion of the
calibration routine the second clocking module 1550 will return to
an OFF or standby mode 151 while the central clocking module 1540
will return to an active mode 1541. These steps will repeat based
on a pre-defined time interval. In some examples the time period
will be the same, but in other examples the time period may be
different or may be based on some algorithm or known relation
between the length of time and the amount of deviation
expected.
[0136] The second clocking module may be linked to the calibration
module that performs the actual calibration routine. The
calibration module may be integrated into the circuitry of the
implanted device. The systems clocking module is able to provide a
central clocking signal that serves as a clock source.
[0137] In some other examples, the systems clocking module is
configured to provide a tick signal that acts as a time keeper.
Periods between device outputs may be defined by the number of tick
counts. While the tick counts accuracy is based upon
characteristics of the circuit parameters, and may be not be as
accurate as some other timing keeping mode, certain methods may be
implemented to accommodate any inaccuracies. For example, tick
counts may be tied to the calibration module, which can be used to
determine the duration of intervals between successive calibration
routines. The start of a calibration routine is initialed by a
signal which is configured to count the ticks from the central
clocking module. The ticks may be counted until the calibration
routine is complete and through a period where the central clocking
module is keeping time. Tick counts may restart based upon the
start of a new calibration routine. Every time the calibration
routine is run, any deviations resulting from the tick counts may
be corrected. In the example of an implantable neurostimulation
device that has wireless recharging capabilities, the tick counts
may be adjusted for accuracy using a more accurate time keeper
located within the wireless transmitter unit. Thus, whenever the
implanted neurostimulation device is being recharged, the tick
counts may be matched with the more time keeping module within the
wireless transmitter unit and any deviations may be corrected. The
benefit of having a tick counting type time-keeping module is that
a patient may move to different time zones without having to modify
potentially salient circadian components of the stimulation
output.
[0138] As alluded to above, the implanted device circuitry or
controller will also be configured to detect a trigger or event
that will commence a calibration routine. The trigger may be an
increase in a threshold voltage or current value. The trigger may
also be a combination or a pattern of changes in the voltage or
current value in more complex arrangement of stimulating
outputs.
[0139] The implantable device will also be configured to provide a
series of signals that will coordinate the switching of the central
clocking module from an active mode to an OFF or standby mode,
while signals are also sent for switching the second clocking
module from an OFF mode to an active mode for the calibration
routine.
[0140] The implantable device may also include programs or
algorithms that will be able to correct for any time drift that may
be detected after the calibration routine is completed. In another
variation, the step of calibrating the central clocking module and
accounting for any deviation may be performed in one step.
[0141] In some non-limiting variations of the clocking calibration
systems and methods, the implantable neurostimulation device may be
able to retain information on the calibration results such as the
amount of drift that the central clocking module has experienced
since the previous calibration routine. This information may be
sent wirelessly to a telecommunication device or may be sent to the
wireless transmitter module during recharging events.
[0142] It should be noted that because the clocking system
described herein is directed to use within an implantable device,
there is minimal temperature variations that may cause further
drifts in the clocking system. Because the implant is in a
temperature stable environment, there may be no need for
temperature compensation. The circuit's wafer to wafer and die to
die variations may be calibrated to a fixed temperature and scaled
to 37.degree. C. during manufacturing of the implantable device,
may be calibrated during the programming of the implantable device,
or during the wireless charging process.
[0143] In yet other variations, the calibration routine and
subsequent correction steps may be in response to a received
voltage or current signal from a sensor via some data communication
link, and compares the received voltage or current signal against a
set of pre-programmed or learned variables and values to determine
if the central clocking module needs to be recalibrated. While the
calibration routine may occur at any time, it may be beneficial to
run the calibration routine when there is no stimulating output
being provided. This would prevent overtaxing the overall circuitry
of the implanted device.
[0144] When a feature or element is herein referred to as being
"on" another feature or element, it can be directly on the other
feature or element or intervening features and/or elements may also
be present. In contrast, when a feature or element is referred to
as being "directly on" another feature or element, there are no
intervening features or elements present. It will also be
understood that, when a feature or element is referred to as being
"connected", "attached" or "coupled" to another feature or element,
it can be directly connected, attached or coupled to the other
feature or element or intervening features or elements may be
present. In contrast, when a feature or element is referred to as
being "directly connected", "directly attached" or "directly
coupled" to another feature or element, there are no intervening
features or elements present. Although described or shown with
respect to one embodiment, the features and elements so described
or shown can apply to other embodiments. It will also be
appreciated by those of skill in the art that references to a
structure or feature that is disposed "adjacent" another feature
may have portions that overlap or underlie the adjacent
feature.
[0145] Terminology used herein is for the purpose of describing
particular embodiments only and is not intended to be limiting of
the invention. For example, as used herein, the singular forms "a",
"an" and "the" are intended to include the plural forms as well,
unless the context clearly indicates otherwise. It will be further
understood that the terms "comprises" and/or "comprising," when
used in this specification, specify the presence of stated
features, steps, operations, elements, and/or components, but do
not preclude the presence or addition of one or more other
features, steps, operations, elements, components, and/or groups
thereof. As used herein, the term "and/or" includes any and all
combinations of one or more of the associated listed items and may
be abbreviated as "/".
[0146] Spatially relative terms, such as "under", "below", "lower",
"over", "upper" and the like, may be used herein for ease of
description to describe one element or feature's relationship to
another element(s) or feature(s) as illustrated in the figures. It
will be understood that the spatially relative terms are intended
to encompass different orientations of the device in use or
operation in addition to the orientation depicted in the figures.
For example, if a device in the figures is inverted, elements
described as "under" or "beneath" other elements or features would
then be oriented "over" the other elements or features. Thus, the
exemplary term "under" can encompass both an orientation of over
and under. The device may be otherwise oriented (rotated 90 degrees
or at other orientations) and the spatially relative descriptors
used herein interpreted accordingly. Similarly, the terms
"upwardly", "downwardly", "vertical", "horizontal" and the like are
used herein for the purpose of explanation only unless specifically
indicated otherwise.
[0147] Although the terms "first" and "second" may be used herein
to describe various features/elements (including steps), these
features/elements should not be limited by these terms, unless the
context indicates otherwise. These terms may be used to distinguish
one feature/element from another feature/element. Thus, a first
feature/element discussed below could be termed a second
feature/element, and similarly, a second feature/element discussed
below could be termed a first feature/element without departing
from the teachings of the present invention.
[0148] Throughout this specification and the claims which follow,
unless the context requires otherwise, the word "comprise", and
variations such as "comprises" and "comprising" means various
components can be co-jointly employed in the methods and articles
(e.g., compositions and apparatuses including device and methods).
For example, the term "comprising" will be understood to imply the
inclusion of any stated elements or steps but not the exclusion of
any other elements or steps.
[0149] In general, any of the apparatuses and methods described
herein should be understood to be inclusive, but all or a sub-set
of the components and/or steps may alternatively be exclusive, and
may be expressed as "consisting of" or alternatively "consisting
essentially of" the various components, steps, sub-components or
sub-steps.
[0150] As used herein in the specification and claims, including as
used in the examples and unless otherwise expressly specified, all
numbers may be read as if prefaced by the word "about" or
"approximately," even if the term does not expressly appear. The
phrase "about" or "approximately" may be used when describing
magnitude and/or position to indicate that the value and/or
position described is within a reasonable expected range of values
and/or positions. For example, a numeric value may have a value
that is +/-0.1% of the stated value (or range of values), +/-1% of
the stated value (or range of values), +/-2% of the stated value
(or range of values), +/-5% of the stated value (or range of
values), +/-10% of the stated value (or range of values), etc. Any
numerical values given herein should also be understood to include
about or approximately that value, unless the context indicates
otherwise. For example, if the value "10" is disclosed, then "about
10" is also disclosed. Any numerical range recited herein is
intended to include all sub-ranges subsumed therein. It is also
understood that when a value is disclosed that "less than or equal
to" the value, "greater than or equal to the value" and possible
ranges between values are also disclosed, as appropriately
understood by the skilled artisan. For example, if the value "X" is
disclosed the "less than or equal to X" as well as "greater than or
equal to X" (e.g., where X is a numerical value) is also disclosed.
It is also understood that the throughout the application, data is
provided in a number of different formats, and that this data,
represents endpoints and starting points, and ranges for any
combination of the data points. For example, if a particular data
point "10" and a particular data point "15" are disclosed, it is
understood that greater than, greater than or equal to, less than,
less than or equal to, and equal to 10 and 15 are considered
disclosed as well as between 10 and 15. It is also understood that
each unit between two particular units are also disclosed. For
example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are
also disclosed.
[0151] Although various illustrative embodiments are described
above, any of a number of changes may be made to various
embodiments without departing from the scope of the invention as
described by the claims. For example, the order in which various
described method steps are performed may often be changed in
alternative embodiments, and in other alternative embodiments one
or more method steps may be skipped altogether. Optional features
of various device and system embodiments may be included in some
embodiments and not in others. Therefore, the foregoing description
is provided primarily for exemplary purposes and should not be
interpreted to limit the scope of the invention as it is set forth
in the claims.
[0152] The examples and illustrations included herein show, by way
of illustration and not of limitation, specific embodiments in
which the subject matter may be practiced. As mentioned, other
embodiments may be utilized and derived there from, such that
structural and logical substitutions and changes may be made
without departing from the scope of this disclosure. Such
embodiments of the inventive subject matter may be referred to
herein individually or collectively by the term "invention" merely
for convenience and without intending to voluntarily limit the
scope of this application to any single invention or inventive
concept, if more than one is, in fact, disclosed. Thus, although
specific embodiments have been illustrated and described herein,
any arrangement calculated to achieve the same purpose may be
substituted for the specific embodiments shown. This disclosure is
intended to cover any and all adaptations or variations of various
embodiments. Combinations of the above embodiments, and other
embodiments not specifically described herein, will be apparent to
those of skill in the art upon reviewing the above description.
* * * * *