U.S. patent application number 15/181973 was filed with the patent office on 2017-02-09 for device and method for biasing lung volume.
This patent application is currently assigned to RMX, LLC. The applicant listed for this patent is RMX, LLC. Invention is credited to Amy M. GOODMAN, Chang Y. LEE, David LIGON, Rose PROVINCE, Amir J. TEHRANI.
Application Number | 20170036017 15/181973 |
Document ID | / |
Family ID | 46323147 |
Filed Date | 2017-02-09 |
United States Patent
Application |
20170036017 |
Kind Code |
A1 |
TEHRANI; Amir J. ; et
al. |
February 9, 2017 |
DEVICE AND METHOD FOR BIASING LUNG VOLUME
Abstract
A device and method is provided for biasing lung volume by
electrically stimulating tissue associated with the diaphragm or
phrenic nerve at a low level.
Inventors: |
TEHRANI; Amir J.; (San
Francisco, CA) ; LIGON; David; (San Francisco,
CA) ; LEE; Chang Y.; (San Jose, CA) ;
PROVINCE; Rose; (San Jose, CA) ; GOODMAN; Amy M.;
(San Francisco, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
RMX, LLC |
San Francisco |
CA |
US |
|
|
Assignee: |
RMX, LLC
San Francisco
CA
|
Family ID: |
46323147 |
Appl. No.: |
15/181973 |
Filed: |
June 14, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13170076 |
Jun 27, 2011 |
9370657 |
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15181973 |
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11271726 |
Nov 10, 2005 |
7970475 |
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13170076 |
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10966472 |
Oct 15, 2004 |
8200336 |
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11271726 |
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10966474 |
Oct 15, 2004 |
8412331 |
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10966472 |
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10966484 |
Oct 15, 2004 |
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10966474 |
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10966421 |
Oct 15, 2004 |
8255056 |
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10966484 |
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10686891 |
Oct 15, 2003 |
8467876 |
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10966421 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/3601 20130101;
A61N 1/3614 20170801; A61B 5/7264 20130101; A61B 5/08 20130101;
A61N 1/3611 20130101; A61B 5/0488 20130101; A61B 5/4818
20130101 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61N 1/08 20060101 A61N001/08; A61B 5/00 20060101
A61B005/00; A61B 5/0488 20060101 A61B005/0488; A61B 5/08 20060101
A61B005/08 |
Claims
1. (canceled)
2. A method of manipulating breathing, comprising: detecting an
onset of a first and subsequent intrinsic breath via an intrinsic
breathing detector within a subject's body; identifying one or more
portions of one or more respiratory cycles internally within the
subject's body, determining whether a respiratory disorder is
detected via a control unit in communication with the intrinsic
breathing detector; upon detecting the respiratory disorder,
delivering an electrically stimulating signal via an electrode to
tissue associated with a phrenic nerve or diaphragm of the subject
to cause a diaphragm response, wherein the electrically stimulating
signal is delivered during at least a first selected existing
intrinsic respiration such that an existing tidal volume which is
present during the selected intrinsic respiration is increased
during the intrinsic breath; and entraining respiration or
inhibiting central respiratory drive for a period of time to treat
or mitigate the respiratory disorder by further delivering the
electrically stimulating signal until respiration is at a first
respiratory rate greater than or equal to an intrinsic respiratory
rate and the respiration is in phase with the electrically
stimulating signal.
3. The method of claim 2 wherein identifying one or more portions
of the one or more respiratory cycles comprises identifying an
inspiration portion.
4. The method of claim 3 wherein delivering an electrically
stimulating signal via an electrode comprises delivering the signal
in synchronization with the inspiration portion.
5. The method of claim 4 further comprising increasing a rate of
the electrically stimulating signal after providing the signal
during the inspiration portion.
6. The method of claim 2 wherein identifying one or more portions
of the one or more respiratory cycles comprises identifying an
exhalation portion.
7. The method of claim 6 wherein delivering an electrically
stimulating signal via an electrode comprises delivering the signal
in synchronization with the exhalation portion.
8. The method of claim 2 wherein delivering an electrically
stimulating signal comprises delivering the electrically
stimulating signal to elicit a sequence of augmented intrinsic
inspirations.
9. The method of claim 2 wherein delivering an electrically
stimulating signal comprises delivering the electrically
stimulating signal to provide a peak flow less than or equal to a
peak flow of an intrinsic breath.
10. The method of claim 2 further comprising placing the electrode
transvenously within the subject prior to delivering an
electrically stimulating signal.
11. The method of claim 2 further comprising stimulating a
hypoglossal nerve such that an upper airway is stimulated in
coordination with the phrenic nerve or diaphragm.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 13/170,076 filed Jun. 27, 2011 (now U.S. Pat.
No. 9,370,657), which is a continuation of U.S. patent application
Ser. No. 11/271,726 filed Nov. 10, 2005 now U.S. Pat. No. 7,970,475
issued Jun. 28, 2011), which is a continuation-in-part of U.S.
patent application No. 10/966,472 filed on Oct. 15, 2004 (now U.S.
Patent No. 8,200,336 issued Jun. 12, 2012); Ser. No. 10/966,474
filed on Oct. 15, 2004 (now U.S. Patent No. 8,412,331 issued Apr.
2,2013); Ser. No. 10/966,484 filed Oct. 15, 2004 (now abandoned);
Ser. No. 10/966,421 filed on Oct. 15, 2004 (now U.S. Pat. No.
8,255,056 issued Aug. 28, 2012); and Ser. No. 10/686,891 filed on
Oct. 15, 2003 (now U.S. Pat. No. 8,467,876 issued Jun. 18, 2013),
the content of each of which is incorporated herein by reference in
its entirety.
FIELD OF INVENTION
[0002] This invention relates to a device and method for treating
respiratory and related disorders.
[0003] There are several factors believed to contribute to the
occurrence of obstructive respiratory events including anatomical
deficiencies, deformities or conditions that increase the
likelihood or occurrence of upper airway collapse; ventilatory
instability; and fluctuations in lung volumes. There is believed to
be a relationship between lung volume and the aperture of the upper
airway with larger lung volume leading to greater upper airway
patency.
[0004] Some obstructive sleep apnea (OSA) patients have increased
upper airway resistance and collapsibility that may contribute to
vulnerability to obstructive respiratory events. The pharyngeal
airway is not supported by bone or cartiligenous structure and
accordingly relies on contraction of the upper airway dilator
muscles to maintain patency. The pharyngeal airway represents a
primary site of upper airway closure.
[0005] Some OSA therapy has been based on a belief that OSA results
from the size and shape of the upper airway muscles or conditions
such as obesity that create a narrowing of the upper air passageway
and a resulting propensity for its collapse.
[0006] In patients with obstructive sleep apnea, various treatment
methods and devices have been used with very limited success.
[0007] CPAP machines have been used to control obstructive sleep
apnea by creating a continuous positive airway pressure (CPAP) at
night. External ventilatory control has been proposed including
sensors that sense a cessation of breathing to determine when an
obstructive sleep apnea event is occurring.
[0008] An implantable stimulator that stimulates the hypoglossal
nerve after sensing an episode of obstructive sleep apnea has been
proposed but has failed to provide satisfactory results in OSA
patients.
[0009] Treating OSA has primarily relied on continuous treatment or
detection of an obstructive respiratory event when it is occurring,
i.e., when the upper air passageway has closed.
[0010] Drug therapy has not provided satisfactory results.
[0011] In central sleep apnea, as opposed to obstructive sleep
apnea, it has been proposed to stimulate a patient's diaphragm or
phrenic nerve to induce breathing where there is a lack of central
respiratory drive. However, such therapy has be contraindicated for
obstructive sleep apnea or respiratory events where there is an
obstructive component, at least in part because stimulating a
patient to breathe when the airway is obstructed is believed to
further exacerbate the collapsing of the airway passage by creating
a pressure that further closes the airway.
[0012] Accordingly, it would be desirable to provide an improved
device and method for treating OSA.
[0013] It would also be desirable to provide treatment for various
other respiratory and related disorders.
SUMMARY OF THE INVENTION
[0014] The present invention provides a novel approach to treating
obstructive sleep apnea and other respiratory related disorders or
conditions.
[0015] In accordance with one aspect of the invention, in a patient
diagnosed with obstructive sleep apnea, tissue associated with the
diaphragm or phrenic nerve is electrically stimulated to prevent
obstructive respiratory events.
[0016] In accordance with one aspect of the invention stimulation
of the diaphragm or phrenic nerve is provided to such obstructive
sleep apnea patients to reduce the occurrence of upper airway
collapse or upper airway flow limitation.
[0017] In accordance with:one aspect of the invention, a device and
method for increasing functional residual capacity (i.e., end
expiratory lung volume) is provided.
[0018] In accordance with one aspect of the invention, a device and
method for increasing upper airway patency is provided.
[0019] In accordance with one aspect of the invention, a device and
method are provided for providing ventilatory stability in an
obstructive sleep apnea patient.
[0020] In accordance with one aspect of the invention, an indicator
of an impending obstructive respiratory event is detected prior to
event onset.
[0021] In accordance with one aspect of the invention, a method for
mitigating (i.e., preventing or lessening) obstructive respiratory
events is provided.
[0022] In accordance with one aspect of the invention, a method and
device is provided for synchronizing stimulation with one or more
portions of an intrinsic breathing cycle.
[0023] In accordance with one aspect of the invention, a device and
method for eliciting deep inspiration while avoiding airway closure
are provided.
[0024] In accordance with one aspect of the invention, a device and
method for normalizing peak flow while increasing tidal volume are
provided.
[0025] In accordance with one aspect of the invention, a device and
method for manipulating exhalation are provided.
[0026] In accordance with one aspect of the invention, a device and
method for entraining breathing are provided.
[0027] In accordance with another aspect of the invention, a device
detects when an obstruction has occurred to a particular extent and
refrains from stimulating if the collapse has occurred to a
particular extent.
[0028] In accordance with another aspect of the invention, a low
level of stimulation is provided for therapeutic effects.
[0029] In accordance with another aspect of the invention, a low
level of stimulation to the diaphragm or phrenic nerve is provided
through or after airway closure to speed up airway opening and
reduce arousal.
[0030] These and other inventions are described herein and/or set
forth in the claims herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIG. 1 is a schematic illustration of a device implanted in
a subject in accordance with the invention.
[0032] FIG. 2 is a schematic illustration of a processor unit of a
sleep breathing disorder treatment device in accordance with the
invention.
[0033] FIG. 3 is a schematic illustration of an external device of
a stimulator in accordance with the invention.
[0034] FIG. 4A is a schematic illustration of respiration of an
exemplary obstructive sleep apnea patient as the patient is going
into an obstructive sleep apnea event.
[0035] FIG. 4B is a schematic illustration of respiration of an
exemplary obstructive sleep apnea patient as the patient is going
into an obstructive sleep apnea event.
[0036] FIGS. 4C and 4D are schematic illustrations respectively of
respiration response and stimulation waveforms illustrating a
stimulation method using a stimulation device according to the
invention in which the obstructive sleep apnea event illustrated in
FIG. 4A is treated with deep inspiration stimulation.
[0037] FIG. 5A is a schematic illustration of respiration of an
exemplary obstructive sleep apnea patient as the patient is going
into an obstructive sleep apnea event.
[0038] FIGS. 5B and 5C are schematic illustrations respectively of
respiration response and stimulation waveforms illustrating a
stimulation method using a stimulation device according to the
invention in which the obstructive sleep apnea event illustrated in
FIG. 5A is treated with deep inspiration stimulation.
[0039] FIGS. 6A, 6B and 6C are schematic illustrations respectively
of airflow, tidal volume and corresponding stimulation waveforms
illustrating a stimulation method using a stimulation device
according to the invention in which stimulation is applied during a
portion of the respiration cycles.
[0040] FIGS. 7A and 7B are schematic illustrations respectively of
tidal volume and corresponding stimulation waveforms illustrating a
stimulation method using a stimulation device according to the
invention in which stimulation is applied during a portion of the
respiration cycles.
[0041] FIGS. 8A and 8B are schematic illustrations respectively of
tidal volume and corresponding stimulation waveforms illustrating a
stimulation method using a stimulation device in which stimulation
is applied in accordance with the invention.
[0042] FIGS. 9A, 9B and 9C are schematic illustrations respectively
of airflow, tidal volume and corresponding stimulation waveforms
illustrating a stimulation method using a stimulation device in
which stimulation is applied in accordance with the invention.
[0043] FIGS. 10A, 10B and 10C are schematic illustrations
respectively of airflow, tidal volume and corresponding stimulation
waveforms illustrating a stimulation method using a stimulation
device in which stimulation is applied in accordance with the
invention.
[0044] FIGS. 11A and 11B are schematic illustrations respectively
of respiration response and stimulation waveforms illustrating a
stimulation method using a stimulation device according to the
invention.
[0045] FIGS. 12A, 12B and 12C are schematic illustrations
respectively of flow and tidal volume respiration response and
stimulation waveforms illustrating a stimulation method using a
stimulation device according to the invention.
[0046] FIGS. 13A and 13B are schematic illustrations respectively
of respiration response and stimulation waveforms illustrating a
stimulation method using a stimulation device according to the
invention.
[0047] FIGS. 14A and 14B are schematic illustrations respectively
of respiration response and stimulation waveforms illustrating a
stimulation method using a stimulation device according to the
invention.
[0048] FIG. 15 is a flow chart illustrating operation of a device
in accordance with the invention.
[0049] FIG. 16A is a schematic of a signal processor of the
processor unit in accordance with the invention.
[0050] FIG. 16B is a schematic example of a waveform of an
integrated signal processed by the signal processor of FIG.
16A.
[0051] FIG. 16C is a schematic EMG envelope waveform.
[0052] FIG. 16D is a schematic waveform corresponding to or
correlated with air flow.
DETAILED DESCRIPTION
[0053] In accordance with one aspect of invention, a method and
device for treating obstructive sleep apnea patients is provided.
According to one embodiment, a device is provided that manipulates
breathing according to one or more protocols, by stimulating the
diaphragm or phrenic nerve to mitigate or prevent obstructive
respiratory events including obstructive sleep apnea or other
events with an obstructive component. The device may comprise a
phrenic nerve of diaphragm stimulator and a sensor configured to
sense a condition of a subject indicating a possibility that an
obstructive respiratory event will occur or is occurring. In
accordance with the invention, obstructive respiratory events are
characterized by a narrowing of the air passageway, typically the
upper air passageway. Examples of obstructive respiratory events
include but are not limited to obstructive sleep apnea, obstructive
hypopnea and other respiratory events with an obstructive
component.
[0054] In another embodiment, stimulation is applied at a low level
through or after an obstructive respiratory event has occurred.
[0055] In addition, in accordance with the invention stimulation
techniques for controlling or manipulating breathing may be used
for therapeutic purposes in other non-OSA patients.
[0056] FIGS. 1 and 2 illustrate a stimulator 20 comprising
electrode assemblies 21, 22, each comprising a plurality of
electrodes 21a-d and 22a-d respectively. The electrode assemblies
21, 22 are implanted in the diaphragm muscle so that one or more of
electrodes. 21a-d and of electrodes 22a-d are approximately
adjacent to one or more junctions of the phrenic nerves 15, 16,
respectively, with the diaphragm 18 muscle. Alternatively or
additionally, electrodes or electrode assemblies may be implanted
on the diaphragm from the thoracic side, at a location along the
phrenic nerve in the thoracic region, neck region or other location
adjacent a phrenic nerve (e.g. transvenously) where stimulating the
phrenic nerve affects breathing and/or diaphragm movement of the
subject. In addition, leads may be subcutaneously placed to
stimulate at least a portion of the diaphragm or phrenic nerve. The
electrode assemblies 21, 22, 31, 32, 41, 42 described herein are
coupled to outputs of a pulse generator and are configured to
deliver electrically stimulating signals to tissue associated with
the implanted electrode assemblies.
[0057] The electrode assemblies 21, 22 (31, 32, 41, 42) may sense
as well as pace or electrically stimulate at the diaphragm muscle
or at the phrenic nerve. Electrode assemblies 21, 22 may be
implanted laparoscopically through the abdomen and into the muscle
of the diaphragm 18 with needles, tissue expanding tubes, cannulas
or other similar devices. The electrode assemblies 21, 22 may be
anchored with sutures, staples, or other anchoring mechanisms. The
electrode assemblies 21, 22 may be surface electrodes or
alternatively intramuscular electrodes. The leads 23, 24 coupling
the electrode assemblies 21, 22 to the control unit 100 are routed
subcutaneously to the side of the abdomen where a subcutaneous
pocket is created for the control unit 100. The electrode
assemblies 21, 22 are each flexible members with electrodes 21a-d,
assembled about 1-20 mm apart from one another and electrodes 22a-d
assembled about 1-20 mm apart from one another. The electrode
assemblies 21, 22 are coupled via leads 23, 24 to control unit 100.
The stimulator 20 further comprises one or more sensors configured
to sense one or more physiologic parameters. For example one or
more sensors such as an accelerometer or movement sensor may sense
information regarding movement pattern of the diaphragm muscles,
intercostal muscles, and rib movement and thus determine overall
respiratory activity and patterns. An electrode or electrodes may
be used to sense the EMG of the diaphragm to determine respiration
parameters. A flow sensor may be implanted in or near the trachea
to sense tracheal air flow. These sensors may be incorporated with
electrode leads 21, 22, 31, 32, 41, 42 or may be separately
implanted or otherwise coupled to the subject.
[0058] The control unit 100 is configured to receive and process
signals corresponding to sensed physiological parameters, e.g.,
flow, nerve activity, diaphragm or intercostal muscle movement,
and/or EMG of the diaphragm 18, to determine the respiratory
parameters of the diaphragm 18. An EMG signal may be used or other
sensed activity may also correspond with either tidal volume or
airflow and may be used to identify different portions of a
respiration cycle. An example of such signal processing or analysis
is described in more detail herein with reference to a sensed
respiration correlated signal, such as an EMG, flow or tidal volume
correlated signal, in FIGS. 16A-16D.
[0059] The electrodes assemblies 21, 22 are coupled via leads 23,
24 to input/output terminals 101, 102 of a control unit 100. The
leads 23, 24 comprise a plurality of electrical connectors and
corresponding lead wires, each coupled individually to one of the
electrodes 21a-d, 22a-d. Alternatively or in addition, electrodes
31, 32 implanted on or near the phrenic nerve in the thoracic
region or electrodes 41, 42 implanted on or near the phrenic nerve
in the neck region. Other locations at or near the phrenic nerve
may be stimulated as well. Electrodes may be placed at or near the
hypoglossal nerve in accordance with a variation of the invention
where stimulation of the diaphragm is coordinated with activation
of upper airway muscles to open the airway passage just prior to
stimulating the diaphragm muscles.
[0060] The control unit 100 is implanted subcutaneously within the
patient, for example in the chest region on top of the pectoral
muscle. The control unit may be implanted in other locations within
the body as well. The control unit 100 is configured to receive
sensed nerve electrical activity from the electrode assemblies 21,
22, (31, 32, 41, 42) corresponding to respiratory effort or other
respiration related parameters of a patient. The control unit 100
is also configured to receive information corresponding to other
physiological parameters as sensed by other sensors. The control
unit 100 delivers stimulation to the nerves 15, 16 or diaphragm as
desired in accordance with the invention. The control unit 100 may
determine when to stimulate as well as specific stimulation
parameters based on sensed information.
[0061] Additional sensors may comprise movement detectors 25, 26,
in this example, strain gauges or piezo-electric sensors included
with the electrode assemblies 21, 22 respectively and electrically
connected through leads 23, 24 to the control unit 100. The
movement detectors 25, 26 detect movement of the diaphragm 18 and
thus the respiration parameters. The movement detectors 25, 26
sense mechanical movement and deliver a corresponding electrical
signal to the control unit 100 where the information is processed
by the processor 105. The movement information correlates to
airflow and may accordingly be used to determine related
respiration parameters.
[0062] Electrodes may be selected from the plurality of electrodes
21a-d and 22a-d once implanted, to optimize the stimulation
response. Electrodes may also be selected to form bipolar pairs or
multipolar groups to optimize stimulation response. Alternatively
electrodes may be in a monopolar configuration. Testing the
response may be done by selecting at least one electrode from the
electrodes in an assembly or any other combination of electrodes to
form at least one closed loop system, by selecting sequence of
firing of electrode groups and by selecting stimulation parameters.
The electrodes may be selected by an algorithm programmed into the
processor that determines the best location and sequence for
stimulation and/or sensing nerve and/or EMG signals, e.g., by
testing the response of the electrodes by sensing respiratory
effort or flow in response to stimulation pulses. Alternatively,
the selection process may occur using an external programmer that
telemetrically communicates with the processor and instructs the
processor to cause stimulation pulses to be delivered and the
responses to be measured. From the measured responses, the external
programmer may determine the optimal electrode configuration, by
selecting the electrodes to have an optimal response to delivery of
stimulation.
[0063] Alternative mapping techniques may be used to place one or
more stimulation electrodes on the diaphragm. Examples of mapping
the diaphragm and/or selecting desired locations or parameters for
desired stimulation responses are described for example in U.S.
application Ser. No. 10/966,484 filed Oct. 15, 2004 and entitled:
SYSTEM AND METHOD FOR MAPPING DIAPHRAGM ELECTRODE SITES; in U.S.
application Ser. No. 10/966,474, filed Oct. 15, 2004 entitled:
BREATHING THERAPY DEVICE AND METHOD; in U.S. application Ser. No.
10/966,472 filed Oct. 15, 2004 entitled: SYSTEM AND METHOD FOR
DIAPHRAGM STIMULATION; U.S. application Ser. No. 10/966,421 filed
Oct. 15, 2004 entitled: BREATHING DISORDER AND PRECURSOR PREDICTOR
AND THERAPY DELIVERY DEVICE AND METHOD; and in U.S. application
Ser. No. 10/686,891 filed Oct. 15, 2003 entitled BREATHING DISORDER
DETECTION AND THERAPY DELIVERY DEVICE AND METHOD, all of which are
fully incorporated herein by reference.
[0064] FIG. 2 illustrates an implantable control unit 100. The
control unit 100 includes electronic circuitry capable of
generating and/or delivering electrical stimulation pulses to the
electrodes or electrode assemblies 21, 22, 31, 32, 41, 42, through
leads 23, 24, 33, 34, 41, 44, respectively, to cause a diaphragm
respiratory response in the patient. For purposes of illustration,
in FIG. 2, the control unit 100 is shown coupled through leads 23,
24 to electrode assemblies 21, 22 respectively. Other leads as
described herein may be connected to inputs 101, 102.
[0065] The control unit 100 comprises a processor 105 for
controlling the operations of the control unit 100. The processor
105 and other electrical components of the control unit are
coordinated by an internal clock 110 and a power source 111 such
as, for example a battery source or an inductive coupling component
configured to receive power from an inductively coupled external
power source. The processor 105 is coupled to a telemetry circuit
106 that includes a telemetry coil 107, a receiver circuit 108 for
receiving and processing a telemetry signal that is converted to a
digital signal and communicated to the processor 105, and a
transmitter circuit 109 for processing and delivering a signal from
the processor 105 to the telemetry coil 107. The telemetry coil 107
is an RF coil or alternatively may be a magnetic coil. The
telemetry circuit 106 is configured to receive externally
transmitted signals, e.g., containing programming or other
instructions or information, programmed stimulation rates and pulse
widths, electrode configurations, and other device performance
details. The telemetry circuit is also configured to transmit
telemetry signals that may contain, e.g., modulated sensed and/or
accumulated data such as sensed EMG activity, sensed flow or tidal
volume correlated activity, sensed nerve activity, sensed responses
to stimulation, sensed position information, sensed movement
information and episode counts or recordings.
[0066] The leads 23, 24 are coupled to inputs 101, 102
respectively, of the control unit 100, with each lead 23, 24
comprising a plurality of electrical conductors each corresponding
to one of the electrodes or sensors (e.g., movement sensor) of the
electrode assemblies 23, 24. Thus the inputs 101, 102 comprise a
plurality of inputs, each input corresponding to one of the
electrodes or sensors. The signals sensed by the electrode
assemblies 21, 22 are input into the control unit 100 through the
inputs 101, 102. Each of the inputs are coupled to a separate input
of a signal processing circuit 116 (schematically illustrated in
FIG. 2 as one input) where the signals are then amplified,
filtered, and further processed, and where processed data is
converted into a digital signal and input into the processor 105.
Each signal from each input is separately processed in the signal
processing circuit 116.
[0067] The EMG/Phrenic nerve sensing has a dual channel sensor. One
corresponding to each lung/diaphragm side. However, sensing can be
accomplished using a single channel as the brain sends signals to
the right and left diaphragm simultaneously. Alternatively, the EMG
or phrenic nerve collective may be sensed using a single channel.
Either a dual channel or single channel setting may be used and
programmed.
[0068] The control unit 100 further includes a ROM memory 118
coupled to the processor 105 by way of a data bus. The ROM memory
118 provides program instructions to the control unit 100 that
direct the operation of the stimulator 20. The control unit 100
further comprises a first RAM memory 119 coupled via a data bus to
the processor 105. The first RAM memory 119 may be programmed to
provide certain stimulation parameters such as pulse or burst
morphology; frequency, pulse width, pulse amplitude, duration and a
threshold or trigger to determine when to stimulate. A second RAM
memory 120 (event memory) is provided to store sensed data sensed,
e.g., by the electrodes of one or more electrode assemblies 21, 22
(EMG or nerve activity), position sensor 121, diaphragm movement
sensors or strain gauges 25, 26, or the accelerometer 122 or other
sensors such as a flow or tidal volume correlated sensors (e.g.
using movement sensors or impedance plethysmography with a sensor
positioned at one or more locations in the body such as on the
control unit 100. These signals may be processed and used by the
control unit 100 as programmed to determine if and when to
stimulate or provide other feedback to the patient or clinician.
Also stored in RAM memory 120 may be the sensed waveforms for a
given interval, and a count of the number of events or episodes
over a given time as counted by the processor 105. The system's
memory will be programmable to store information corresponding to
breathing parameters or events, stimulation delivered and
responses, patient compliance, treatment or other related
information. These signals and information may also be compiled in
the memory and downloaded telemetrically to an external device 140
when prompted by the external device 140.
[0069] An example of the circuits of the signal processing circuit
116 corresponding to one or more of the sensor inputs is
illustrated schematically in FIG. 16A. A sensor input signal
correlating or corresponding to EMG, tidal volume or flow is input
into an amplifier 130 that amplifies the signal. The signal is then
filtered to remove noise by filter 131. The amplified signal is
rectified by a rectifier 132, is converted by an A/D converter 133
and then is integrated by integrator 134 to result in an integrated
signal from which respiratory information can be ascertained. A
flow correlated signal may be input through A/D converter 133a and
then input through the integrator 134. The signal output of the
integrator 134 is then coupled to the processor 105 and provides a
digital signal corresponding to the integrated waveform to the
processor 105. A tidal volume correlated signal may also be input
to the signal processing circuit through AID converter 134a at the
output of the integrator 134. The signal output of the integrator
134 is coupled to a peak detector 135 that determines when the
inspiration period of a respiratory cycle has ended and an
expiration cycle has begun. The signal output of the integrator 134
is further coupled to a plurality of comparators 136, 137. The
first comparator 136 determines when respiration has been detected
based on when an integrated signal waveform amplitude has been
detected that is greater than a percentage value of the peak of an
intrinsic respiratory cycle or another predetermined amount (comp
1), for example between 1-25% of the intrinsic signal. In this
example, the comparator is set at a value that is 10% of the
waveform of an intrinsic respiratory cycle. The second comparator
137 determines a value of the waveform amplitude (comp 2) when an
integrated signal waveform amplitude has been detected that is at a
predetermined percentage value of the peak of an intrinsic
respiratory cycle or another predetermined amount, for example
between 75%-100% of the intrinsic signal. In this example, the
comparator is set at a value that is 90% of the waveform of an
intrinsic respiratory cycle. From this value and the comp 1 value,
the slope of the inspiration period (between 10% and 90% in this
example) may be determined. This slope may provide valuable
diagnostic information as it shows how quickly a patient
inhales.
[0070] In the case of a signal correlating to flow that is
integrated or a signal correlated to tidal volume, after (or when)
the peak detector detects the end of an inhalation period and the
beginning of an exhalation period, the third comparator 138
determines an upper value for the waveform amplitude during active
exhalation period, for example between 100% and 75% of the peak
value detected by the peak detector 135. Then a lower value (comp
4) of the waveform during the exhalation period is determined by
the fourth comparator 139, which compares the measured amplitude to
a predetermined value, e.g. a percentage value of the peak
amplitude. In this example, the value is selected to be 10% of the
peak value. In one embodiment this value is selected to roughly
coincide with the end of a fast exhalation period. From comp 3 and
comp 4 values, the slope of the exhalation period (between 10% and
90% in this example) may be determined. This slope may provide
valuable diagnostic information as it shows how quickly a patient
exhales.
[0071] A non-integrated flow signal may also be used, for example
in conjunction with EMG to detect airway closure where EMG is
present in the absence of flow.
[0072] FIG. 16B illustrates two sequential integrated waveforms of
exemplary integrated signals corresponding to two serial
respiratory cycles. An inspiration portion 172 may be observed
using an EMG, flow or tidal volume correlated signal. An exhalation
period 176 may be observed using a flow or tidal volume correlated
signal. The waveform 170 has a baseline 170b, inspiration cycle
171, a measured inspiration cycle 172, a point of 10% of peak
inspiration 173 (comp 1), a point of 90% of peak of inspiration 174
(comp 2), a peak 175 where inspiration ends and exhalation begins,
and exhalation cycle 176 a fast exhalation portion 177 of the
exhalation cycle 176, a 90% of peak exhalation point 178 (comp 3),
a 10% of peak exhalation point 179 (comp 4), an actual respiratory
cycle 180 and a measured respiratory cycle 181. The second waveform
182 is similarly shaped. The 10% inspiration 183 of the second
waveform 182 marks the end of the measured respiratory cycle 181,
while the 10% point 173 of the waveform 170 marks the beginning of
the measured respiratory cycle 181.
[0073] FIG. 16C illustrates a schematic EMG envelope corresponding
to an inspiration portion e.g., 172 of a respiration cycle. FIG.
16D illustrates a schematic flow correlated signal corresponding to
a respiration cycle.
[0074] In FIG. 3 a circuit for an external device 140 is
illustrated. The external device 140 comprises a processor 145 for
controlling the operations of the external device. The processor
145 and other electrical components of the external device 140 are
coordinated by an internal clock 150 and a power source 151. The
processor 145 is coupled to a telemetry circuit 146 that includes a
telemetry coil 147, a receiver circuit 148 for receiving and
processing a telemetry signal that is converted to a digital signal
and communicated to the processor 145, and a transmitter circuit
149 for processing and delivering a signal from the processor 145
to the telemetry coil 146. The telemetry coil 147 is an RF coil or
alternatively may be a magnetic coil depending on what type of coil
the telemetry coil 107 of the implanted control unit 100 is. The
telemetry circuit 146 is configured to transmit signals to the
implanted control unit 100 containing, e.g., programming or other
instructions or information, programmed stimulation protocols,
rates and pulse widths, electrode configurations, and other device
performance details. The telemetry circuit 146 is also configured
to receive telemetry signals from the control unit 100 that may
contain, e.g., sensed and/or accumulated data such as sensed
information corresponding to physiological parameters, (e.g.,
sensed EMG activity, sensed nerve activity, sensed responses to
stimulation, sensed position information, sensed flow, or sensed
movement information). The sensed physiological information may be
stored in RAM event memory 158 or may be uploaded and through an
external port 153 to a computer, or processor, either directly or
through a phone line or other communication device that may be
coupled to the processor 145 through the external port 153. The
external device 140 also includes ROM memory 157 for storing and
providing operating instructions to the external device 140 and
processor 145. The external device also includes RAM event memory
158 for storing uploaded event information such as sensed
information and data from the control unit, and RAM program memory
159 for system operations and future upgrades. The external device
also includes a butler 154 coupled to or that can be coupled
through a port to a user-operated device 155 such as a keypad input
or other operation devices. Finally, the external device 140
includes a display device 156 (or a port where such device can be
connected), e.g., for display visual, audible or tactile
information, alarms or pages.
[0075] The external device 140 may take or operate in, one of
several forms, e.g. for patient use, compliance or monitoring; and
for health care provider use, monitoring, diagnostic or treatment
modification purposes. The information may be downloaded and
analyzed by a patient home unit device such as a wearable unit like
a pager, wristwatch or palm sized computer. The downloaded
information may present lifestyle modification, or compliance
feedback. It may also alert the patient when the health care
provider should be contacted, for example if there is
malfunctioning of the device or worsening of the patient's
condition.
[0076] Other devices and methods for communicating information
and/or powering stimulation electrodes as are know in the art may
be used as well, for example a transcutaneously inductively coupled
device may be used to power an implanted device.
[0077] According to one aspect of the invention, the stimulator
operates to stimulate and/or manipulate breathing to mitigate
(i.e., avoid or reduce effects of) an obstructive respiratory event
by stimulating the phrenic nerve, diaphragm or associated tissue
according to one or more protocols, to elicit a respiratory
response. Examples of such stimulation protocols are described
herein with reference to FIGS. 4A-16D. In accordance with another
aspect of the invention, such stimulation is provided prior to the
onset of an obstructive respiratory event or prior to airway
obstruction to prevent an obstructive respiratory event from
occurring or the airway from fully closing. In accordance with
another aspect of the invention, stimulation is provided at a low
level following obstructive sleep apnea or effective airway
closure.
[0078] In accordance with one aspect of the invention as described
with respect to FIGS. 4A-4D, 5A-5C, 7A-7B, 8A-8B, 9A-9C, 10A-10C
and 12A-12B, stimulation of the phrenic nerve or diaphragm is
provided to increase functional residual capacity, i.e., end
expiratory volume, at least until onset of a subsequent respiration
cycle. In accordance with the invention, an increased functional
residual capacity is believed to assist in maintaining an airway
passage open to a sufficient degree to prevent or reduce airway
collapse that results in an obstructive respiratory event.
[0079] In accordance with another aspect of the invention, as
described with respect to FIGS. 4A-4D, 5A-5B, 6A-6B, 10A-10C,
11A-11B, 12A-12B or 14A-14B, stimulation of the phrenic nerve or
diaphragm is provided to increase tidal volume sufficiently to
increase upper airway patency. It is believed that increasing the
tidal volume may contribute to stiffening the upper airway.
Preferably the same or a lower peak flow with respect to intrinsic
flow is provided to avoid an increase in negative pressure applied
to the upper airway that would decrease upper airway patency.
Therapy may be delivered to increase flow in the case where flow is
below normal. In cases where flow is normal, or limited by
obstruction, tidal volume may be increased through extension of the
inspiration duration. An upper airway hysteresis effect may also
occur where the volume of a breath is increased above a normal
tidal volume and the stiffening of the upper airway during
inspiration does not return entirely to a relaxed resting state. It
is accordingly additionally believed that an upper airway
hysteresis effect would stiffen the upper air passageway for
subsequent breaths and will thereby prevent or mitigate airway
narrowing or collapse that results in obstructive sleep apnea.
[0080] In accordance with one aspect of the invention, as described
with respect to FIGS. 9A-9C, 11A-11B, 13A-13B and 14A-14B,
stimulation is provided to create ventilatory stability and to
thereby reduce fluctuations in the upper airway passage muscles
that may lead to upper airway collapse where ventilatory drive is
low or unstable. "Ventilatory instability is defined herein to mean
varying breathing rate and/or tidal volume outside of normal
variations." Ventilatory stability associated with obstructive
respiratory events, as opposed to periodic breathing or
Cheynes-Stokes respiration, include, for example, variations in
breathing rate and/or tidal volume associated with sleep onset,
change in sleep state, and REM sleep.
[0081] In accordance with another aspect of the invention, as
described with respect to FIGS. 4A-4D, 6A-6C, 9A-9C and 10A-10C,
11A-11B, 12A-12B, and 14A-14B, stimulation of the phrenic nerve or
diaphragm is provided during intrinsic breathing during or at the
end of an intrinsic inspiration portion of a breathing cycle. For
purposes of the invention herein, the intrinsic cycle may be
detected near onset of inspiration. Other portions of a breathing
cycle may be identified for breathing stimulation. Alternatively,
the beginning of the breathing cycle or a portion of the breathing
cycle may be predicted, e.g., based on a typical breathing pattern
of an individual patient.
[0082] A stimulation signal may be provided during inspiration of
intrinsic breathing for various purposes. In accordance with a
variation of the invention, stimulation is provided during
intrinsic inspiration to provide initial and more gradual control
of breathing according to a protocol. Then, breathing control
protocols may be applied so that airway closure due to stimulation
is avoided. Tidal volume is increased gradually so as to balance
out an increase in upper airway resistance that can occur with
stimulation during intrinsic inspiration. Stimulation of breathing
during intrinsic inspiration in accordance with variations of the
invention is configured to contribute to creating the effect of
increasing functional residual capacity. In some variations of the
invention, stimulation during intrinsic breathing is configured to
stiffen the upper airway, thereby increasing upper airway patency.
Stimulating during inspiration in accordance with a protocol of the
invention may also increase upper airway hysteresis. In one
embodiment, breathing is stimulated at least in part during
intrinsic inspiration so that the resulting tidal volume is greater
than intrinsic normal volume, while peak flow is maintained near
normal peak flow to avoid upper airway closure. Stimulating during
intrinsic inspiration may also be used to normalize breathing in an
obstructive sleep apnea patient and to increase ventilatory
stability associated with airway obstructions. Stimulating at least
in part during intrinsic inspiration may increase inspiration
duration which may allow increase of tidal volume without
significantly increasing the peak flow. (Increasing peak flow may
increase the possibility of airway closure.) According to one
embodiment, peak flow is provided at, near or below intrinsic peak
flow.
[0083] While stimulating breathing during intrinsic inspiration is
described herein in use with a device and method of treating
obstructive sleep apnea, other breathing or related disorders may
be treated by stimulating breathing during intrinsic inspiration in
accordance with another aspect of the invention.
[0084] In accordance with another aspect of the invention and as
illustrated in FIGS. 4A-4D, and 5A-5C the phrenic nerve or
diaphragm is stimulated to provide deep inspiration therapy to a
subject. Deep inspiration therapy involves stimulating a breath
that is of a greater tidal volume than a normal breath. According
to a preferred embodiment, deep inspiration stimulation provides a
breath having a greater inspiration duration than that of a normal
breath. Rather than substantially increasing peak flow or rather
than increasing the magnitude of diaphragm contraction, the
increase in inspiration duration to increase tidal volume is
believed to reduce the likelihood of airway closure with
stimulation. Deep inspiration stimulation may be provided
intermittently throughout the night or a portion of the night while
a patient sleeps, thus preventing an obstructive respiratory event.
While deep inspiration therapy is described herein in use with a
device and method of treating obstructive sleep apnea, other
breathing or related disorders may be treated by deep inspiration
therapy.
[0085] In accordance with another aspect of the invention as
described with respect to FIGS. 6A-6B, 7A-7B, 8A-8B, 9A-9C, 10A-10C
and 12A-12B, the exhalation cycle is manipulated to provide a
therapeutic effect. According to one aspect of the invention,
increased functional residual capacity is provided by manipulating
the exhalation phase. Manipulation of the exhalation phase may be
provided using stimulation during the exhalation phase. The
exhalation phase may also otherwise be manipulated in length or
duration.
[0086] In accordance with another aspect of the invention as
described with respect to FIGS. 7A-7B 8A-8B, 9A-9C, and 10A-10C, a
low level stimulation is applied during all or a portion of the
respiration cycle. Among other therapeutic effects such stimulation
may increase functional residual capacity. Such low level
stimulation may be directed to provide an increased tidal volume
during a rest phase of a respiration cycle by sustaining a low
level contraction of the diaphragm. Typically such low level
stimulation would be lower than the relative threshold for
eliciting breathing. This level may vary from patient to patient
and may be determined on an individual basis. It may also depend on
electrode type and placement. Typically the stimulation is lower
than 8 mA.
[0087] In accordance with another aspect of the invention, as
described with respect to FIGS. 9A-9C, 12A-12B, 13A-13B, and
14A-14B, stimulation of the phrenic nerve or diaphragm is provided
to control breathing. According to one aspect of the invention,
breathing is controlled either by inhibiting respiratory drive,
entraining breathing or other mechanisms. Controlling breathing
according to one variation comprises stimulating to control or
manipulate the central respiratory drive. Controlling breathing may
include taking over breathing to control one or more parameters of
a stimulated breath. Entraining breathing may include stimulating
at a rate greater than but close to, or equal to the intrinsic
respiratory rate until the central pattern generator activates the
respiration mechanisms, which includes those of the upper airway,
in phase with the stimulation. As an alternative or in addition,
inspiration duration may be increased with respect to the total
respiration cycle or exhalation. While controlling breathing is
described herein in use with a device and method of treating
obstructive sleep apnea, other breathing or related disorders may
be treated by controlling breathing in accordance with another
aspect of the invention.
[0088] According to another aspect of the invention stimulation is
used to provide ventilatory stability. Examples of providing
ventilatory stability are shown in FIGS. 9A-9C, 10A-10B, 11A-11B,
13A-13B and 14A-14B. Ventilatory stability may be provided by
stimulating breathing to increase a tilling tidal volume towards
that of a normal breath. Ventilatory stability may also be provided
by controlling breathing in a manner that creates stability.
Ventilatory stability may also be provided by entraining breathing.
Instability in ventilatory rate that indicates the onset of
obstructive sleep apnea may be treated by controlling breathing for
a preset period of time as described with respect to FIGS. 9A-9B,
13A-13B or FIGS. 14A-14B. Instability in ventilatory rate may also
be treated by normalizing tidal volume using stimulation as
described with respect to FIGS. 10A-10B or 11A-11B.
[0089] Referring to FIGS. 4A-4D, stimulation and respiration
waveforms illustrating a method using a device in accordance with
one aspect of the invention are illustrated. A device and method
creates increased functional residual capacity and upper airway
patency by providing deep inspiration. In this particular
embodiment, deep inspiration is provided by stimulating during a
portion of an inspiration cycle. Stimulation may extend beyond the
duration of an intrinsic breath. The stimulation is provided to
increase tidal volume by extending the duration of the inspiration
cycle. (While preferably maintaining peak flow at or near intrinsic
peak flow, i.e. normalizing flow.) In accordance with a protocol,
stimulation through one or more electrodes associated with the
diaphragm or phrenic nerve is provided to cause the diaphragm to
contract to cause a deep inspiration breath. Stimulation may be
provided when a characteristic preceding an obstructive respiratory
event is detected. For example, if erratic breathing occurs or if
the tidal volume drops below a given threshold level, then
stimulation is provided. The resulting breath comprises a deep
inhalation breath (i.e., a greater tidal volume than a normal,
intrinsic breath.) A deep inspiration breath may then be repeated
periodically to prevent further drop in tidal volume by increasing
the functional residual capacity and creating upper airway
stiffening. The device may also be programmed to repeat the deep
breath a given number of times before ceasing the stimulation.
[0090] One possible characteristic of breathing in obstructive
sleep apnea patients is a decreasing tidal volume. The ultimate
closure of an air passageway in an obstructive sleep apnea event
thus may be preceded by a gradual decrease in ventilatory volume.
Another possible characteristic of breathing in obstructive sleep
apnea patients is an erratic breathing pattern. In a patient who is
diagnosed with obstructive sleep apnea, respiration may be
monitored using EMG or other sensors that sense respiration
parameters corresponding to tidal volume or flow (for example,
diaphragm movement which corresponds to airflow may be sensed;
impedance plethysmography may be used; or flow itself may be sensed
using a sensor implanted in the trachea.) FIGS. 16A-16D illustrate
monitoring or detection of various aspects or parameters of
respiration on a breath by breath basis. Tidal volume is monitored
and a decrease in tidal volume characteristic (FIG. 4A) or an
erratic breathing pattern (FIG. 4B) in an obstructive sleep apnea
patient is detected. (Monitored tidal volume as used herein may
also include a monitored tidal volume correlated signal). Estimated
minute ventilation (i.e., determined by multiplying respiratory
rate times volume of a breath) may also be used to determine the
impending onset of an obstructive respiratory event.
[0091] For purposes of detecting a threshold volume on a
breath-by-breath basis or in real time, a programmed threshold may
be set. The threshold value may be determined when initializing the
device as the value at or below which preventative or mitigating
treatment is required or is otherwise optimal. This value may be
programmed into the device. A minimum safety threshold value may
also be established below which stimulation is inhibited to prevent
airway closure. As such, the minimum safety threshold may be set as
a value sufficiently above a tidal volume where stimulation
treatment if provided would further close an air passageway.
[0092] When monitoring tidal volume, the area under the inspiration
flow curve or EMG envelope of an individual breath may be monitored
to determine tidal volume of a breath. The tidal volume is compared
to a threshold value for a particular patient. Other parameters may
be used to identity when tidal volume has dropped below a
predetermined threshold, for example baseline tidal volume rate
variance over a period of time may be monitored and compared to a
normal variance. The normal variance may be determined on a
patient-by-patient basis and programmed into the device.
[0093] FIG. 4A illustrates a breathing pattern where a decrease in
tidal volume ultimately ends in an obstructive sleep apnea event.
Accordingly, tidal volume of intrinsic breaths 411-415 of an
obstructive sleep apnea patient is shown in FIG. 4A. The tidal
volume of breaths 411-415 gradually decreases until the airway
narrows ultimately leading to an airway obstruction. An obstructive
respiratory event occurs with total airway closure after breath
415. An obstructive respiratory event may also be an airway
narrowing, e.g. hypopnea. An obstructive respiratory event may be
detected by monitoring a decrease in tidal volume, for example as a
predetermined percentage of normal or intrinsic tidal volume. The
threshold 450 below which treatment is to be provided by the device
is shown in FIGS. 4A-4D. FIG. 4D illustrates a stimulation protocol
corresponding to the resulting tidal volume waveforms of FIG.
4C.
[0094] FIG. 4C illustrates tidal volume of a patient treated using
a deep inspiration stimulator. The stimulator detects the drop in
tidal volume (breath 413) below a threshold level as described
above with respect to FIGS. 4A-4B. During the subsequent breath
414, stimulation 434 (schematically illustrated as an envelope of a
burst of pulses) is provided by the stimulator to provide a deep
inspiration breath 424 with the breath 414. The deep inspiration
breath 424 comprises a breath that has a tidal volume greater than
the tidal volume of a normal or intrinsic breath. After one or more
deep inspiration breath stimulations, the tidal volume is expected
to return to normal or close to normal, e.g. at breaths 425-429.
Synchronization is provided whereby the onset of inspiration is
detected and stimulation is provided during the breath. According
to one variation, a tidal volume that is greater than or equal to a
predetermined percentage of a normal inspiration is detected (e.g.
10% of tidal volume as described with respect to FIGS. 16A-16D).
Then when the onset of the next inspiration is detected,
stimulation is provided. Additional periodic delivery of deep
inspiration paced breaths may be provided synchronously or
asynchronously with the intrinsic breathing, to prevent or mitigate
drops in tidal volume. In accordance with this aspect of the
invention, as illustrated in FIG, 4D an additional pacing pulse or
burst of pulses 439 is provided to stimulate deep inspiration
breath 419. Thus, the therapy described with reference to FIG. 4D
may prevent a further drop in tidal volume, thereby reducing the
occurrence of obstructive respiratory events or other breathing
related disorders.
[0095] FIGS. 5A-5C illustrate use of a deep inspiration stimulator
in accordance with the invention. FIG. 5A illustrates a breathing
pattern where a decrease in tidal volume ultimately ends in an
obstructive respiratory event. Accordingly, tidal volume of
intrinsic breaths 511-515 of an obstructive sleep apnea patient is
shown in FIG. 5A with the airway ultimately closing after breath
515. In FIG. 5A, no treatment is provided. Other pre-obstructive
breathing characteristics may also be used to determine when an OSA
event is likely to be imminent.
[0096] A threshold 550 below which treatment is to be provided by
the device is shown in FIGS. 5A and 5B. This threshold may be
determined in a manner similar to that described with respect to
FIGS. 4A-4C. FIG. 5C illustrates a stimulation protocol
corresponding to the resulting tidal volume waveforms of FIG. 5B.
FIG. 5B illustrates the tidal volume of a patient treated using a
deep inspiration stimulator who would otherwise have had a
breathing pattern shown in FIG. 5A. The stimulator detects the drop
in tidal volume (breath 513) below a threshold level 550 in a
manner similar to that described above with respect to FIGS. 4A-4D.
Prior to what would have been the subsequent breath 514, i.e. at
some point during the intrinsic exhalation period or rest period,
the stimulator provides stimulation 533 to elicit a deep
inspiration breath 523 (FIG. 5B). The deep inspiration breath 523
comprises a breath with a tidal volume greater than the tidal
volume of an intrinsic or normal breath. Preferably, the peak flow
remains relatively normal while inspiration duration increases thus
increasing tidal volume. After one or more deep inspiration breath
stimulations, the tidal volume returns to normal, e.g., at breaths
524-525. At breaths 526, 527 a slight decrease in respiratory drive
is shown with a decreased tidal volume. Periodic delivery of deep
inspiration breaths may be provided to prevent or mitigate drops in
tidal volume. In accordance with this aspect of the invention, as
illustrated in FIG. 5C an additional pacing pulse or burst of
pulses 538 is provided prior to the onset of the next intrinsic
breath to stimulate deep inspiration breath 528 which is then
followed by a normal breath 529. The deep inspiration breaths 523
or 528 are intended to increase the functional residual capacity of
the lung and/or enhance upper airway potency. Thus, the therapy may
prevent further drop in tidal volume, thereby reducing the
incidence of obstructive sleep apnea or other breathing related
disorders.
[0097] FIGS. 6A-6B illustrate stimulation and inspiration waveforms
corresponding to a variation of stimulation device and method of
the invention. The stimulation protocol of FIGS. 6A-6B provides
stimulation at the end of an inspiration cycle increasing
inspiration duration, thereby increasing tidal volume. A resulting
normalized peak flow and increased tidal volume is believed to
stiffen or lengthen the upper airway and may create an upper airway
hysteresis effect Increased tidal volume may provide more time and
volume for gas exchange. Among other effects, normalized peak flow
and increased tidal volume are believed to prevent airway collapse
attributable to obstructive sleep apnea.
[0098] FIG. 6A illustrates normal inspiration duration 610 of an
intrinsic breath and increased inspiration duration 620 that would
result from stimulation 650 shown in FIG. 6B. Stimulation 650 is
provided at the end of an inspiration period for a predetermined
amount of time T.sub.6 to maintain flow and prolong inspiration for
the additional period of time T.sub.6. The end of the inspiration
period may be determined in a manner as described with reference to
FIGS. 16A-16D herein. The time T.sub.6 may be selected and/or
programmed into the device. The time may be determined to elicit a
desired response. A short stimulation period, for example, as short
as 0.1 seconds may be used.
[0099] FIGS. 7A-7B illustrate stimulation and inspiration waveforms
corresponding to a variation of a stimulation device and method of
the invention. The stimulation protocol of FIGS. 7A-7B provides low
level stimulation at the beginning or the end of an exhalation
portion of a respiration cycle, or at some time within the
exhalation portion of the respiration cycle. This is believed to
preserve lung volume prior to the next inspiration. The
manipulation of the exhalation cycle is thus believed to increase
functional residual capacity. FIG. 7A illustrates tidal volume 730
that would result from stimulation 750 shown in FIG. 7B.
Stimulation 750 is provided at an end portion of an exhalation
cycle to preserve some volume 740 for the next inspiration cycle
thus increasing the functional residual capacity. The end of the
exhalation cycle may be determined by determining the end of
inspiration and then based on a known respiration rate, estimating
the time of the end of the exhalation cycle. Alternatively, flow
correlated respiration parameters may be sensed and the desired
portion of the exhalation cycle may be determined. FIGS. 16A-16D
illustrate manners for determining portions of a illustrate
stimulation and inspiration waveforms corresponding to a variation
respiration cycle.
[0100] FIGS. 8A-8B of a stimulation device and method or the
invention. The stimulation protocol of FIG. 8B provides a low level
of a continuous stimulation to cause the diaphragm to remain
slightly contracted, thereby increasing functional residual
capacity. FIG. 8B illustrates stimulation provided while FIG. 8A
illustrates tidal volume. As shown, the tidal volume is elevated
during the end portion of the exhalation cycle 840 (FIG. 8A)
relative to end expiratory tidal volume before the stimulation.
[0101] FIGS. 9A-9C illustrate stimulation and inspiration waveforms
corresponding to a variation of a stimulation device and method of
the invention. The stimulation protocol provides a combination of
therapies or protocols including increasing functional residual
capacity and controlling breathing. The stimulation protocols
manipulate exhalation and control breathing. The stimulation
protocol of FIGS. 9A-9C provides a low current stimulation 950 as
shown in FIG. 9C during the exhalation phase of a respiration cycle
and a stimulated breath 951 delivered at the end of exhalation. The
stimulated breath 951 is provided at a higher rate R2 than the
intrinsic rate R1. The stimulation 950 is applied between the end
of inspiration cycles 920, 921, 922 and the onset of the next
inspiration cycles, 921, 922, 923 respectively to increase
functional residual capacity. Stimulation 951 produces inspiration
cycles 920, 921, 922, 923. Flow waveforms 930, 931, 932, 933
respectively of respiration cycles 920, 921, 922, 923 are shown in
FIG. 9A. Tidal volume waveforms 940, 941, 942, 943 respectively of
respiration cycles 920, 921, 922, 923 are shown in FIG. 9B.
[0102] FIGS. 10A-10B illustrate stimulation and inspiration
waveforms corresponding to a variation of a stimulation device and
method of the invention. Stimulation is provided during the
inspiration cycle in a manner shown in FIGS. 7A-7B to increase
inspiration duration and tidal volume (with normalized peak flow)
in order to stiffen the upper airway. Also, a low level stimulation
is provided to increase lung capacity at the end of inspiration and
until the beginning of the next inspiration cycle to increase the
functional residual capacity. A first intrinsic respiration cycle
1020 is illustrated. At the onset of exhalation 1021 of the
respiration cycle 1020, a low level stimulation 1050 is applied
until the onset of the inspiration cycle of the next respiration
cycle 1022. At the detection of the onset of the next respiration
cycle 1022 (as described in FIGS. 16A-16D), stimulation 1055 is
provided. The stimulation 1055 is applied at least in part during
the inspiration cycle 1022. The corresponding tidal volumes 1040,
1042 of respiration cycles 1020, 1022 respectively are illustrated
in FIG. 10A. The corresponding flows 1030, 1032 of respiration
cycles 1020, 1022 respectively are shown in FIG. 10B.
[0103] Referring to FIGS. 11A and 11B, stimulation and inspiration
waveforms illustrate a stimulation device and method of the
invention. Stimulation is provided in a manner similar to that
described with reference to FIGS. 4A-4D. In accordance with FIGS.
11A and 11B, stimulation is provided to prevent or mitigate
obstructive sleep apnea by stabilizing the tidal volume. FIG. 11A
schematically shows the tidal volume as sensed by EMG sensors and
illustrates the intrinsic breathing 1111-1117 of a subject, as well
as the resulting breathing 1124, 1125. FIG. 11B illustrates the
stimulation pulse envelopes 1160 of stimulation applied to the
diaphragm or phrenic nerve of a subject in accordance with one
aspect of the invention. Referring to FIG. 11A, the tidal volume
from intrinsic breathing gradually decreases (1111, 1112) until it
falls below a threshold level 1150 (1113-1115) and then resumes
normal tidal volume (1116-1117) after treatment. After breath 1113
is detected below threshold level 1150, a stimulation pulse 1160 is
provided during and in synchronization with the subsequent breath
1114, 1115 to thereby provide the resulting breath. The resulting
breaths have waveforms 1124, 1125 with tidal volumes increased to a
level of normal breathing. According to one variation, stimulation
is provided with the goal of stabilizing or normalizing breathing.
After stimulating for a given period of time or number of breaths,
breathing is monitored to determine if it is normalized (for
example with breaths 1116, 1117) at which time the stimulation may
be discontinued.
[0104] FIGS. 12A-12B illustrate stimulation and inspiration
waveforms corresponding to a variation of a stimulation device and
method of the invention. The stimulation protocol of FIGS. 12A-12B
provides a long rising stimulation during at least the inspiration
portion of a respiration cycle to increase inspiration time of the
cycle with respect to expiration time (or total percentage of the
cycle that corresponds to inspiration). Using breathing control
therapy to lengthen the inspiratory duration, expiratory time is
reduced and the baseline relaxation lung volume is not completely
restored, leading to an increased functional residual capacity. The
stimulation protocol thereby manipulates or shortens the length of
the exhalation portion of the respiration cycle. In addition, the
respiration rate is increased to shorten the exhalation portion of
the respiration waveform. Thus, the protocol is directed to
increasing the functional residual capacity of the lungs by
manipulating the expiration phase of the respiration cycle.
[0105] FIG. 12A illustrates flow and FIG. 12B illustrates
corresponding stimulation. Referring to FIG. 12A a first intrinsic
breath 1210 is shown with an intrinsic inspiration volume V.sub.II
and an intrinsic expiration volume V.sub.IE. Prior to time
T.sub.12A, breathing may be entrained (for example, as described
with respect to FIGS. 13A and 13B herein) at a rate slightly faster
than the intrinsic rate but at approximately a normal tidal volume
and waveform 1210. Thereafter, stimulation 1240 is applied during a
rest period (i.e. at an end portion of the exhalation phase) of a
respiration cycle 1220 following breath 1210. The stimulation is
provided using a long rising pacing pulse so that the respiration
cycle is lengthened by a time T.sub.12B to prevent full expiration
before the next inspiration cycle of the next breath 1230 which is
provided by stimulation 1250. Stimulation 1250 is provided at a
rate slightly faster than the previous stimulation 1240. Thus,
exhalation is shortened, preventing exhalation portion 1260, and
thus increasing the functional residual capacity of the lungs.
[0106] Referring to FIGS. 13A-13B, stimulation and respiration
waveforms illustrating a stimulation method using a stimulation
device in accordance with one aspect of the invention are
illustrated. According to FIGS. 13A-13B, breathing is stabilized by
stimulating to control or manipulate breathing. FIGS. 13A-13B
illustrate a variation of a technique for controlling
breathing.
[0107] FIG. 13A illustrates the flow of air representing
respiration waveforms over time. Breathing control may be used for
a number of different purposes. It may be done with or without
sensing a condition that indicates a respiratory disturbance is
present or occurring. It may be done for a predetermined period of
time or during certain times of day or during certain sleep cycles.
It may be done to stabilize breathing.
[0108] For example, if tidal volume falls below a predetermined
threshold, stimulation may begin. Stimulation may also be provided
periodically or at times of greater vulnerability to obstructive
sleep apnea or other disorders associated with breathing disorders.
FIG. 13B illustrates envelopes 1340 of stimulation pulses provided
to control breathing during the course of stimulation. FIG. 13A
illustrates the breaths 1360 resulting from the stimulation
illustrated in FIG. 13B.
[0109] According to this embodiment, the stimulator first takes
over breathing by providing stimulation 1340 (as illustrated in
FIG. 13B) at a time during an end portion 1320 of the exhalation
phase of an intrinsic respiration cycle, prior to the onset of the
next respiration cycle (As illustrated in FIG. 13A). The
stimulation 1340 is provided at a rate greater than the intrinsic
rate, i.e., where the cycle length T1 is less than the intrinsic
cycle length T1+x. As illustrated, the duration of the intrinsic
respiration cycle is T.sub.1+x. The duration of the respiration
cycles of the stimulated breathing begins at T.sub.1 to take over
breathing. After a period of time of taking over breathing, the
respiration cycle length is then gradually increased to T1+m, t1+n,
and T1+o where m<n<o<x and where o approaches x in value.
Breathing is thereby controlled and ventilation is accordingly
stabilized.
[0110] According to one aspect of the invention, breathing is
believed to be controlled by stimulating for a period of time at a
rate greater than but close to the intrinsic respiratory rate.
Breathing may be controlled through inhibition of the central
respiratory drive or entrainment. In order to entrain breathing,
stimulation may be provided until the central pattern generator
activates the respiration mechanisms, which includes those of the
upper airway, in phase with the stimulation through various
feedback mechanisms. It is believed that breathing may be entrained
when the central respiratory drive is conditioned to adapt to
stimulation. When breathing is entrained, it may be possible to
further slow respiration rate or the respiration cycle length so
that it is longer than the intrinsic length 1320.
[0111] Some methods for controlling breathing are described for
example in U.S. application Ser. No. 10/966,474, filed Oct. 15,
2004 and incorporated herein by reference.
[0112] Referring to FIGS. 14A and 14B inspiration flow waveforms
and stimulation pulse envelope waveforms are shown corresponding to
a variation of a stimulation device and method of the invention. In
accordance with this variation, the stimulation device stimulates
during intrinsic breaths 1411, 1412, 1413 to provide resulting
breaths 1421, 1422, 1423. The intrinsic breaths occur at a rate B1
as illustrated in FIG. 14A. The first stimulation 1451 is applied
at a delay D1 from the onset of intrinsic breath 1411. The next
stimulation 1452 is provided at a delay D2 from the onset of
intrinsic breath 1412 and the subsequent stimulation pulse 1453 is
provided at a delay D3 from the onset of intrinsic breath 1413. The
time between the first and second stimulation 1451 and 1452 is
T.sub.1+DELTA. a while the time between the second and third
stimulation 1452 and 1453 is T.sub.1, i.e., shorter. Thus
stimulation is provided gradually closer and closer to the onset of
stimulation to gently take over breathing with stimulation at least
in part during intrinsic inspiration. The stimulation 1453 is
essentially synchronous with the start of the intrinsic inspiration
1413, to create the resulting breath 1423. Stimulation may be
delivered at this rate for a period of time. Then the next stimulus
1454 is delivered at a rate faster than normal at a respiration
cycle length timed to thereby elicit paced breath 1424. The next
stimulus 1455 is delivered at the interval T2, to induce another
paced breath 1425, and this may be continued for some time in order
to control breathing. This may lead to the entrainment of the
central respiratory control system. Also, rate may be increased
gradually until no intrinsic breaths occur between the paced
breaths. When control of respiratory rate is achieved (and possibly
entrainment), if a slowing of the breathing rate is desired, the
pacing rate can be decreased gradually as shown schematically in
the Figure by stimuli delivered at a cycle length of T2+x, followed
by T2+2x, inducing paced breaths 1426 and 1427. It is believed that
if entrained, if desired, the stimulation rate may bring the
respiration rate slower than the intrinsic rate and tidal volume
may be manipulated. After a period of time or after breathing has
been controlled as desired, the intrinsic breathing may be allowed
to resume, for example, as shown with breath 1418. The patient may
be weaned off stimulation, for example, as described herein.
[0113] In accordance with another aspect of the invention, the
phrenic nerve or diaphragm may be stimulated using the low level
stimulation as described herein, through an OSA event after
obstructive sleep apnea event has occurred.
[0114] The stimulation described or shown herein may be comprised
of several stimulation parameters. For example a burst of pulses
may form a square pulse envelope or may ramp up or down in
amplitude or a combination thereof. The frequencies may vary or may
be varied depending upon a desired result. In accordance with one
embodiment, the burst frequency ranges between 5-500 Hz and more
preferably between 20-50 Hz. However, other frequency ranges may be
used as desired. Low level pulses or continuous stimulation may
comprise stimulation at about 8 mA or less or may be determined on
a case-by-case basis. However, other amplitudes and frequencies may
be used as desired. The stimulation may be monophasic or may be
biphasic. Stimulation may be provided in response to sensing
respiration or other parameters. Alternatively, stimulation may be
provided periodically or during specific times, for example during
sleep, during sleep stage transitions, or during non-REM sleep.
[0115] Stimulation may also be slowly phased out. That is the
patients may be weaned from stimulation slowly. In general, when
paced breathing is ongoing, and the therapy is to be stopped, it
may be beneficial to wean the patient off the therapy to avoid
creating apnea that may lead to obstructions or arousals. Weaning
off would involve a gradual decrease in rate, until an intrinsic
breath is detected. Once an intrinsic breath is detected, the
device would discontinue pacing and would return to monitoring
mode. An example of a protocol for weaning a patient off from
stimulation is described, for example, in U.S. application Ser. No.
10/686,891 filed Oct. 15, 2003. Other variations of weaning
patients off are also possible.
[0116] FIG. 15 is a flow chart illustrating operation of a system
or device in accordance with the invention. An implanted device is
initialized during an initialization period 1510. During the
initialization period, among other things, the thresholds may be
set up for triggering or inhibiting therapy. The thresholds may be
set up by observing patient breathing over time. Therapy modalities
may also be chosen, for example by testing various stimulation
protocols to optimize therapy. For example, information obtained
from one or more breaths can be used to set pacing parameters for
subsequent therapies. Examples of data that can be obtained from
one or a series of breaths include: rate, tidal volume, inspiration
duration, flow parameters, peak flow, and/or duty-cycle. In the
case of paced breathing therapies or breathing control (and
possible entrainment), the rate of intrinsic breathing could be
measured, and then paced breathing could be delivered, for example,
at a faster rate than the measured rate. As another example, one
could measure the inspiration duration of previous intrinsic
breaths, and induce a breath to create an inspiration duration
longer (or shorter) than the previous intrinsic breaths. During
initialization or when updating the device, test stimulation
signals and measured responses may be used to determine appropriate
stimulation parameters.
[0117] During operation, the therapy is turned on 1520. This may be
done automatically or manually. Therapy is delivered 1530 as is
determined to be appropriate for a particular patient in accordance
with one or more protocols, for example as described herein.
[0118] While the invention has been described with respect to
treating obstructive sleep apnea, various aspects of the invention
are not limited to use in obstructive sleep apnea patients. The
various techniques for controlling breathing as disclosed herein
may be used in other therapeutic applications where controlling
breathing is desired, for example in various breathing related
disorders.
[0119] For example, stimulating breathing during intrinsic
inspiration may be useful in any treatment involving control of
breathing. Stimulating during intrinsic inspiration may be used as
a technique to gradually begin to control or manipulate breathing
parameters such as breathing rate, inspiration duration and tidal
volume. Simulation during intrinsic breathing may be used with a
number of breathing control protocols to initiate control of
breathing, e.g., to gradually take over or to entrain breathing and
to gradually control or manipulate breathing parameters.
[0120] The various techniques used to increase functional residual
capacity maybe used in connection with any therapy where an
increase in functional residual capacity results in a desired
benefit.
[0121] Likewise, therapy described herein that stiffen the upper
airway may also be used in any therapy for a breathing related
disorder where the effects of improving upper airway patency are
beneficial.
[0122] Similarly the techniques for controlling or entraining
breathing as described herein may be used in other therapeutic
applications where controlling or entraining breathing is
desired.
[0123] Similarly, techniques for creating ventilatory stability as
described herein may be used in other therapeutic application where
stabilization is beneficial.
[0124] Stimulation may be provided at various times during sleep or
various sleep stages or sleep transitions, including but not
limited to, for example: prior to sleep, at sleep onset, upon
detection of dropping tidal volume, upon detection of transition
into REM or non-REM or during REM or non-REM sleep, or upon changes
in breathing patterns, including but not limited to breathing
rate.
[0125] The various stimulation protocols described herein may be
combined in a variety of manners to achieve desired results.
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