U.S. patent application number 12/004932 was filed with the patent office on 2008-07-24 for method for treating a subject having neuromuscular impairment of the diaphragm.
Invention is credited to Rose Province, Amir J. Tehrani.
Application Number | 20080177347 12/004932 |
Document ID | / |
Family ID | 46329668 |
Filed Date | 2008-07-24 |
United States Patent
Application |
20080177347 |
Kind Code |
A1 |
Tehrani; Amir J. ; et
al. |
July 24, 2008 |
Method for treating a subject having neuromuscular impairment of
the diaphragm
Abstract
A method for treating a subject is provided where at least two
types of electrical stimulation are provided to cause diaphragm
contraction. At least one type of stimulation is configured to bias
lung volume of a subject. The stimulation method may include
without being limited to a method to treat a subject having
neuromuscular impairment of the diaphragm. The stimulation method
may also include without being limited to a method to treat a
subject who has been diagnosed with central sleep apnea.
Inventors: |
Tehrani; Amir J.; (San
Francisco, CA) ; Province; Rose; (San Jose,
CA) |
Correspondence
Address: |
RMX, L.L.C.
P.O. Box 3550
Los Altos
CA
94024
US
|
Family ID: |
46329668 |
Appl. No.: |
12/004932 |
Filed: |
December 21, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11981342 |
Oct 31, 2007 |
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12004932 |
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11480074 |
Jun 29, 2006 |
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11981342 |
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11271726 |
Nov 10, 2005 |
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11480074 |
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10966484 |
Oct 15, 2004 |
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11271726 |
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10966474 |
Oct 15, 2004 |
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10966484 |
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10966421 |
Oct 15, 2004 |
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10966474 |
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10966472 |
Oct 15, 2004 |
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10966421 |
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10686891 |
Oct 15, 2003 |
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10966472 |
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60876632 |
Dec 22, 2006 |
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Current U.S.
Class: |
607/42 |
Current CPC
Class: |
A61B 5/4818 20130101;
A61B 5/08 20130101; A61B 5/7264 20130101; A61N 1/3601 20130101;
A61B 5/389 20210101 |
Class at
Publication: |
607/42 |
International
Class: |
A61N 1/00 20060101
A61N001/00 |
Claims
1. A method of treating a subject who has been diagnosed with
central sleep apnea comprising: providing a first electrical
stimulation to cause a diaphragm contraction to thereby elicit a
lung volume bias; and subsequently providing a second electrical
stimulation to elicit at least one breath.
2. The method of claim 1 wherein the first electrical stimulation
is provided after detection of a decreased respiratory drive.
3. The method of claim 1 wherein the second electrical stimulation
is provided after detection of central apnea.
4. The method of claim 1 wherein at least a portion of the first
stimulation overlaps at least a portion of the second
stimulation.
5. A method for treating a subject having neuromuscular impairment
of the diaphragm comprising: providing a first electrical
stimulation to elicit a diaphragm contraction and thereby elicit a
lung volume bias immediately prior to: providing a breathing assist
stimulation to elicit diaphragm contraction to increase ventilation
of a subject.
6. The method of claim 5 wherein the subject having a neuromuscular
impairment is a subject having paralysis impairing diaphragm
movement.
7. The method of claim 5 wherein the subject having a neuromuscular
impairment is a subject having ALS.
8. The method of claim 5 wherein the step of providing breathing
assist stimulation comprises providing stimulation configured to
increase tidal volume of the subject.
9. The method of claim 8 wherein the step of providing stimulation
configured to increase tidal volume of the subject comprises
providing stimulation to augment intrinsic breathing.
10. The method of claim 8 wherein the step of providing stimulation
configured to increase tidal volume comprises providing stimulation
to create breaths.
11. A method for treating a subject comprising; providing a first
electrical stimulation to elicit a diaphragm contraction and
thereby elicit a lung volume bias immediately prior to or after:
providing a second therapeutic electrical stimulation to elicit a
diaphragm contraction wherein the second therapeutic electrical
stimulation is selected from a group comprising: breathing
augmentation stimulation, deep inspiration therapy, increasing
inspiration duration; and manipulating duty cycle of inspiration
with respect to a respiration cycle.
12. The method of claim 11 further comprising the step of providing
the first electrical stimulation during the second electrical
stimulation.
Description
RELATED APPLICATION DATA
[0001] This application claims priority of U.S. Provisional
Application Ser. No. 60/876,632 filed Dec. 22, 2006 and is a
continuation in part of U.S. application Ser. No. 11/981,342 filed
Oct. 31, 2007, which is a continuation in part of U.S. application
Ser. No. 11/480,074 filed Jun. 29, 2006, which is a continuation in
part of U.S. application Ser. No. 11/271,726 filed Nov. 10, 2005
which is a continuation in part of U.S. application Ser. No.
10/966,484 filed Oct. 15, 2004; U.S. application Ser. No.
10/966,474, filed Oct. 15, 2004; U.S. application Ser. No.
10/966,421, filed Oct. 15, 2004; and U.S. application Ser. No.
10/966,472 filed Oct. 15, 2004 which are continuations in part of
U.S. application Ser. No. 10/686,891 filed Oct. 15, 2003 entitled:
BREATHING DISORDER DETECTION AND THERAPY DELIVERY DEVICE AND
METHOD
BACKGROUND
[0002] Devices and methods for creating a lung volume bias and/or
increasing functional residual capacity have been disclosed in one
or more of the following application: U.S. application Ser. No.
11/981,342 filed Oct. 31, 2007, which is a continuation in part of
U.S. application Ser. No. 11/480,074 filed Jun. 29, 2006, which is
a continuation in part of U.S. application Ser. No. 11/271,726
filed Nov. 10, 2005 which is a continuation in part of U.S.
application Ser. No. 10/966,484 filed Oct. 15, 2004; U.S.
application Ser. No. 10/966,474, filed Oct. 15, 2004; U.S.
application Ser. No. 10/966,421, filed Oct. 15, 2004; and U.S.
application Ser. No. 10/966,472 filed Oct. 15, 2004 which are
continuations in part of 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 incorporated herein by
reference in their entirety. One or more of these applications also
disclose a number of different applications for creating lung
volume bias and/or increasing functional residual capacity.
SUMMARY
[0003] The present invention provides a device and method for
providing electrical stimulation to elicit a diaphragm response.
Among other things, one aspect of the invention provides a device
and method for electrical stimulation to cause a lung volume bias.
According to one aspect a lung volume bias augments lung volume
during exhalation or inspiration and exhalation. According to one
aspect, biased lung volume is superimposed on respiration.
According to another aspect biased lung volume may be provided by
causing a long slow increase in volume. According to one aspect the
lung volume bias provides a therapeutic increase in airway
traction. According to one aspect, lung volume bias provides a
changing in lung volume over which intrinsic breathing may occur.
In accordance with one aspect of the invention electrical
stimulation may be provided directly or indirectly to the phrenic
nerve and/or diaphragm of a subject. In accordance with one aspect
of the invention treatment may be provided for a number of
diseases, disorders and conditions that may relate to, have
co-morbidities with, affect, be affected by respiratory or lung
health status, respiration, ventilation, or blood gas levels. Such
diseases and disorders may include but are not limited to
obstructive respiratory disorders, upper airway resistance
syndrome, snoring, obstructive apnea; central respiratory
disorders, central apnea; hypopnea, hypoventilation, obesity
hypoventilation syndrome other respiratory insufficiencies,
inadequate ventilation or gas exchange, chronic obstructive
pulmonary diseases; asthma; emphysema; chronic bronchitis;
circulatory disorders; hemodynamic disorders; hypertension; heart
disease; chronic heart failure; cardiac rhythm disorders; obesity
or injuries in particular affecting breathing or ventilation.
[0004] Among other things, an aspect of the invention provides a
device and method for electrical stimulation to increase functional
residual capacity of a subjects lungs. Such increase in functional
residual capacity according to one aspect may be a lung volume
bias. The invention also provides a device and method for
electrical stimulation to create caudal traction on the upper
airway by increasing lung volume or functional residual capacity,
thereby stabilizing the airway and/or improving upper airway
patency. The invention also provides stimulation techniques for
avoiding diaphragm fatigue, improving patient comfort, reducing
undesired affects of stimulation such as upper airway closure,
selecting stimulation parameters, selecting therapy type providing
individualized treatment and/or diagnostics, adjusting stimulation,
and/or improving battery life. The present invention also provides
preventative or ameliorative treatment for diseases disorders or
conditions. The present invention also provides improved
stimulation for one or more diseases, disorders or conditions.
[0005] In accordance with one aspect of the invention slow gradual
ramping up of stimulation is provided over the course of a period
of time greater than a period of one inspiration cycle, or over the
course of time spanning multiple breaths, to gradually increase
lung volume, provide a lung volume bias, and/or increase functional
residual capacity. Stimulation may be ramped down as well. Among
other things, the gradual ramping of stimulation may provide
greater patient comfort, reduce a likelihood of arousal from
stimulation, or may reduce sudden change in negative pressure as
seen by to upper airway and thereby avoid upper airway closure
during stimulation. Thus according to the invention stimulation
provides a slow and/or gradual increase in lung volume. One or more
stimulation parameters may be ramped including, e.g., pulse
amplitude, frequency, pulse width, burst duration and/or burst
frequency.
[0006] According to one aspect of the invention stimulation is
alternated between hemidiaphragms to allow rest or prevent
adaptation. Stimulation may be separately applied or otherwise
controlled to each hemidiaphragm, by turning on or off stimulation
or by changing stimulation parameters for one or both of the
hemidiaphragms. The timing may also be separately controlled.
Initialization, selection or application of stimulation parameters
for each diaphragm may also be separate.
[0007] Similarly, stimulation may be alternated or rotated from one
electrode or electrode pair (or group) to another in a multiple
electrode assembly. Stimulation may be altered on the same
hemidiaphragm or opposite hemidiaphragms.
[0008] Stimulation to each hemidiaphragm or each electrode (or
electrode pair) may be ramped up and down separately or, for
example one may be ramped up while the other is ramped down to
provide a smoother transition and produce gradual changes in lung
volume or other respiration parameters when switching stimulation
from one hemidiaphragm to the other or from one electrode or
electrode pair to another. Also one side may be stimulated first
and then the other side to provide a more gradual increase in
volume. Similarly a gradual ramp down may be provided by reducing
stimulation to one hemidiaphragm and then the other.
[0009] In accordance with one aspect of the invention, stimulation
is provided by varying one or more stimulation parameters, e.g.,
amplitudes, frequencies, pulse widths and/or burst durations or
burst frequencies, to avoid fatigue or adaptation. Such stimulation
parameters may be within a desired range or may be altered to
provide an optimization of diaphragm rest and diaphragm activation.
Such stimulation protocol may be generally open loop where a
predetermined program or sequence is used for preset time periods
to stimulate and also provide rest. Stimulation may be cycled
through different amplitudes and/or frequencies or other
parameters. Such stimulation protocol may also be generally closed
loop where stimulation parameters are adjusted based on feedback
indicating rest is needed or that adaptation is occurring.
Stimulation may also be adjusted or cycled on or off depending upon
a patient status, such as, for example, sleep state status,
response to therapy, or other condition or status. Such protocol
may be either open loop, closed loop or a combination thereof,
e.g., wherein stimulation is provided for a period of time
according to a protocol and then sensing is used to periodically
determine stimulation and response status. For example, after a
period of stimulation, detection or sensing may be used to
determine if breathing is continuing to be stabilized after
stimulation. Stabilized ventilation may be detected, for example,
using methods and devices that determine variations in lung volume,
tidal volume, functional residual capacity, flow, or other
respiration parameter. Stimulation may be provided again when
breathing stabilization has fallen off.
[0010] Stimulation may be individualized on a patient by patient
basis by determining individual patient response to stimulation to
result in an optimal or preferred functional residual lung volume
or a sustained lung volume bias, to get a desired result. Detection
as well as stimulation may be optimized or selected on a patient by
patient basis where patient stability markers are determined e.g.
using polysomnography data (for device initialization and/or device
programming updating). Such initialization may provide a
determination of functional residual capacity or change in
functional residual capacity resulting from stimulation.
Accordingly, a baseline functional residual capacity is sensed or
observed as a reference point, stimulation is provided and response
or change in FRC produced by the stimulation is sensed or observed.
Functional residual capacity may be observed before, during and
after stimulation. Such observation of stimulation and response may
be while subject is awake or during sleep. A number of
polysomnography markers may be used to determine effectiveness of
stimulation such as: (volume changes, stability of flow, FRC,
volume, arousals, arousals in response to or due to stimulation).
To reduce arousals due to stimulation, stimulation parameters may
be modified such as stimulation frequency, stimulation amplitude or
stimulation ramping. Also stimulation to one or other hemidiaphragm
may be adjusted to provide a more gradual affect from stimulation.
Other information may be used to determine adaptation to
stimulation where the stimulation may be either more effective or
less effective, or fatigue where the stimulation is less effective.
Modification of stimulation parameters may be provided in response
to such fatigue or adaptation. Such device initialization may be
provided with external or temporary sensors, for example in a
polysomnography study, or where appropriate when the patient is
awake. Such device initialization may also be provided with sensors
and/or detection incorporated into the stimulation device or its
peripherals. Also such device initialization may be provided
periodically or on an ongoing basis during the term of device
usage. The device may be programmed to adjust stimulation
parameters or protocol during the device usage term.
[0011] Such initialization may also be used to select a type of
stimulation or stimulation protocol that is most effective for an
individual's particular disorder, disease or breathing/disordered
breathing. Such initialization may also be used to initialize
detection
[0012] Various detection algorithms may also be incorporated into
the device to detect various conditions and/or trigger therapy. The
device may be programmed to respond with adjustment, switching or
turning on or off of stimulation based on various detections.
[0013] According to one aspect of the invention, an increase in FRC
or a lung volume bias may be used for therapeutic purposes prior to
materialization of an apnea event where breathing instability is
present, even when no event is present or clearly imminent.
According to one aspect, if then a central or obstructive apnea
does occur, the device may either turn off stimulation, or provide
stimulation according to a different protocol. Occurrence of an
event or pattern of events may trigger stimulation to prevent
future events.
[0014] Detection may comprise detecting flow limitations or
unstable breathing that are not at an apnea level and turning on
diaphragm stimulation to provide stability, improving gas exchange
or ventilation to reduce flow limitation or stabilize breathing.
For example obstructive apnea patients, unstable breathing or
degree of flow limitation may be detected, or other indicators of a
likelihood of obstruction occurring, for example the previous
occurrence or pattern of occurrence of events. Stimulation may be
accordingly be provided to increase functional residual capacity or
provide a lung volume bias. If obstructive apnea occurs,
stimulation may be turned off. Turning off stimulation may also be
used to increase upper airway patency with increased exhalation or
to increase airflow. Where a patient suffers from central apnea or
mixed apneas, absent such event stimulation may be provided to
increase functional residual capacity or provide a lung volume bias
to regulate or manipulate gas exchange, improve ventilation and/or
stabilize breathing to reduce conditions that lead to overshooting
of respiratory drive as well as improving upper airway patency. If
central apnea is detected then paced breathing may be provided
until normal breathing resumes. After an arousal, a pattern of
instability or flow limitations, or apnea event has occurred,
stimulation may be turned on to prevent subsequent events. In
accordance with this aspect of the invention, detection of apnea
events, flow limitations or other respiratory disorders or
instability may trigger turning on or off of therapy. Therapy may
then be provided for a period of time or based on a detected
respiratory state or otherwise controlled in a closed loop
system.
[0015] According to one aspect of the invention, stimulated lung
volume bias is a supplemental increase in lung volume that may be
provided with intrinsic, paced or augmented breathing. It may also
be provided with other breathing control scenarios.
[0016] According to another aspect of the invention, a first type
of stimulation may be provided and subsequently switched to another
type of stimulation. Such switch in stimulation type may be based
on, for example, a determination of effectiveness or lack of
effectiveness of the first type of stimulation or a change in
condition.
[0017] According to one aspect of the invention a biased lung
volume may be provided before, during and/or after other diaphragm
stimulation among other things, to help avoid upper airway closure.
Such other diaphragm stimulation or stimulation types may include
for example, paced breathing, augmented breathing, deep inspiration
stimulation, breathing control or manipulation of breathing, as
well as high frequency contraction stimulation. According to
another aspect of the invention a biased lung volume may be
provided before other diaphragm stimulation among other things, to
help avoid upper airway closure. According to another aspect of the
invention a biased lung volume may be provided after other
diaphragm stimulation among other things, to help avoid upper
airway closure. According to another aspect of the invention a
biased lung volume may be provided throughout other stimulation or
a portion of other stimulation.
[0018] According to another aspect of the invention stimulation
providing a biased lung volume may be turned off to increase upper
airway patency where the sudden change in pleural pressure or
outflow creates an opening of the upper airway prior to the next
breath.
[0019] These and other aspects of the invention are set forth in
the specification and claims herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] FIGS. 1A to 1C schematically illustrate lung volume,
stimulation of the right hemidiaphragm and stimulation of the left
hemidiaphragm respectively with a ramped up stimulation for
creating lung volume bias and a ramped down stimulation.
[0021] FIGS. 2A to 2C schematically illustrate lung volume, a first
stimulation signal at a first electrode and a second stimulation
signal at a second electrode illustrating gradual ramping of
stimulation and alternating stimulation at different locations.
[0022] FIGS. 3A to 3C schematically illustrate lung volume, a first
stimulation signal at a first electrode and a second stimulation
signal at a second electrode illustrating gradual ramping of
stimulation and alternating stimulation at different locations.
[0023] FIG. 4 is a flow diagram illustrating device initialization
to achieve desired increase in FRC and/or sustained lung volume
bias.
[0024] FIGS. 5A to 5C are flow diagrams illustrating detection and
therapy in accordance with the invention.
[0025] FIGS. 6A to 6C respectively schematically illustrate EMG,
EMG envelope and tidal volume of a subject over varying degrees of
airway patency.
[0026] FIG. 6D is a power spectral density diagram for three EMG
signals corresponding to varying degrees of airway patency.
[0027] FIG. 6E is a schematic diagram of EMG envelope under
different conditions.
[0028] FIGS. 7A to 7C schematically illustrate flow, lung volume
and stimulation respectively in accordance with one aspect of the
invention.
[0029] FIGS. 8A to 8C schematically illustrate lung volume under
different conditions and using different levels of bias
stimulation.
[0030] FIGS. 9A to 9D schematically illustrate flow, EMG envelope,
lung volume and stimulation respectively in accordance with an
aspect of the invention.
[0031] FIGS. 10A to 10C schematically illustrate snoring (in
decibels) tidal volume and stimulation respectively in accordance
with an aspect of the invention.
DETAILED DESCRIPTION
[0032] In accordance with one aspect of the invention slow gradual
ramping up of stimulation is provided over the course of a period
of time greater than a period of one inspiration cycle, or over the
course of time spanning multiple breaths. For example, while not
intending to be limited thereto, ramping may be provided over a
period of about 5 to 60 seconds. The ramping up described may
reduce arousals or waking from patient detection of stimulation. It
is believed that among other things, ramping may improve patient
comfort by producing more gradual diaphragm contraction and more
gradual pressure changes. It is also believed that ramping may
reduce the possibility of obstruction that may occur with a greater
negative thoracic pressure.
[0033] Ramping describe herein may be titrated base on patient
feedback such as sensation, or in a sleep lab.
[0034] FIGS. 1A to 1C illustrate a lung volume bias stimulation
being ramped up and then down over a period of multiple breaths.
The amplitude, frequency, pulse duration, burst duration, and/or
burst frequency, may be modulated or ramped or slowly increased as
schematically illustrated in FIGS. 1B and 1C. FIG. 1B illustrates a
stimulation signal envelope 130 for stimulation of a right
hemidiaphragm. The stimulation signal envelope 130 comprises a
ramped portion 135 schematically illustrating the ramping up of the
right hemidiaphragm signal over a plurality of breaths 121. FIG. 1B
further illustrates a ramped portion 139 schematically illustrating
ramping down of the right hemidiaphragm signal over a plurality of
breaths 121. FIG. 1C illustrates a stimulation signal envelope 150
for stimulation of a left hemidiaphragm. The stimulation signal
envelope 150 comprises a ramped portion 155 schematically
illustrating the ramping up of the left hemidiaphragm signal over a
plurality of breaths 121. FIG. 1C further illustrates a ramped
portion 159 schematically illustrating ramping down of the left
hemidiaphragm signal over a plurality of breaths 121. Stimulation
to the right and left hemidiaphragms are generally synchronized as
illustrated in FIGS. 1B and 1C. FIG. 1A illustrates a corresponding
lung volume. Breaths 121 as illustrated in FIG. 1A are intrinsic
breaths. However, ramping up and down of lung volume bias
stimulation as illustrated in FIGS. 1B and 1C may also be used
during paced breathing. A baseline lung volume 120 (initial
functional residual capacity) is shown prior to stimulation. During
the period of ramping stimulation 122, functional residual capacity
is gradually increased from the baseline 120. Once the stimulation
has been ramped, stimulation is leveled off for period 123.
Stimulation is then ramped down for period 124 where functional
residual capacity gradually decreases.
[0035] The gradual ramping periods 122 and 124 may be for a period
greater than a normal intrinsic inspiration period or over a period
spanning a plurality of breaths. While a lung volume bias is
illustrated, other stimulation may be ramped up or down in
accordance with an aspect of the invention.
[0036] In accordance with one aspect of the invention, a gradual
increase in the duty cycle of bias situation may also be provided.
The duty cycle may be independent of intrinsic respiration or may
be synchronized with breathing.
[0037] In accordance with one aspect of the invention slow gradual
ramping up of stimulation is provided with the stimulation offset
between two hemidiaphragms or between two or more electrodes or
electrode pairs. FIGS. 2A to 2C illustrate a lung volume bias
stimulation being ramped up over a period of multiple breaths with
ramping offset between hemidiaphragms. Stimulation may also be
ramped down in an offset manner. The amplitude, frequency, pulse
duration, burst duration, and/or burst frequency, may be modulated
or ramped or slowly increased as schematically illustrated in FIGS.
2B and 2C. FIG. 2B illustrates a stimulation signal envelope 230
for stimulation of a right hemidiaphragm. The stimulation signal
envelope 230 comprises a ramped portion 235 schematically
illustrating the ramping up of the right hemidiaphragm signal for a
period 222 over a plurality of breaths 221. FIG. 2C illustrates a
stimulation signal envelope 250 for stimulation of a left
hemidiaphragm. The stimulation signal envelope 250 comprises a
ramped portion 255 schematically illustrating the ramping up of the
left hemidiaphragm signal for a period 223 over a plurality of
breaths 221. Stimulation to the right and left hemidiaphragms are
offset as illustrated in FIGS. 2B and 2C. The periods 222 and 223
are offset from each other but overlap in time. Alternatively, the
periods 222, 223 may be sequential. FIG. 2A illustrates a
corresponding lung volume. Breaths 221 as illustrated in FIG. 2A
are intrinsic breaths. However, ramping up and down of lung volume
bias stimulation as illustrated in FIGS. 2B and 2C may also be used
during paced breathing. A baseline lung volume 220 (initial
functional residual capacity) is shown prior to stimulation. During
the periods of ramping stimulation 222, 223 functional residual
capacity is gradually increased from the baseline 220. Once the
stimulation has been ramped, stimulation is leveled off at both
hemi-diaphragms for a period of time. The gradual ramping periods
222 and 223 may individually or in the aggregate be for a period
greater than a normal intrinsic inspiration period or over a period
during a plurality of breaths. While offset ramping is shown with
respect to electrodes at two different hemidiaphragms, such offset
ramping may be provided with any two or more electrodes or
electrode pairs, whether positioned on the same hemidiaphragm or
not. Offset ramping may be provided with more than two electrodes
or electrode pairs where ramping occurs in the aggregate for a
period greater than that of a normal intrinsic inspiration or for a
period spanning multiple breaths.
[0038] The gradual ramping periods 222 and 223 may be for a period
greater than a normal intrinsic inspiration period or over a period
spanning a plurality of breaths. While a lung volume bias is
illustrated, other stimulation may be ramped up or down in
accordance with an aspect of the invention. Offset stimulation may
also be used to prevent fatigue by resting stimulated portions of
the diaphragm or phrenic nerve while maintaining stimulation
on.
[0039] In accordance with one aspect of the invention switching of
stimulation from one hemidiaphragm, electrode or electrode pair to
another is provided. According to one aspect, stimulation is
provided in a manner that maintains a therapeutic diaphragm
contraction. FIGS. 3A to 3C illustrate a lung volume bias
stimulation over a period of multiple breaths with ramping up of
one hemidiaphragm and ramping down of the other hemidiaphragm. The
amplitude, frequency, pulse duration, burst duration, and/or burst
frequency, may be modulated or ramped or slowly increased as
schematically illustrated in FIGS. 3B and 3C. FIG. 3B illustrates a
stimulation signal envelope 330 for stimulation of a right
hemidiaphragm. The stimulation signal envelope 330 comprises a
ramped portion 335 schematically illustrating the ramping down of
the right hemidiaphragm signal for a period 322 over a plurality of
breaths 321. FIG. 3C illustrates a stimulation signal envelope 350
for stimulation of a left hemidiaphragm. The stimulation signal
envelope 350 comprises a ramped portion 355 schematically
illustrating the ramping up of the left hemidiaphragm signal for a
period 323 over a plurality of breaths 321. The periods 322 and 323
overlap in time. FIG. 3A illustrates a corresponding lung volume.
Breaths 321 as illustrated in FIG. 3A are intrinsic breaths.
However, ramping up and down of lung volume bias stimulation as
illustrated in FIGS. 3B and 3C may also be used during paced
breathing. A baseline lung volume 320 (initial functional residual
capacity) is shown prior to stimulation. During the periods of
ramping respectively down and up of stimulation 322, 323,
functional residual capacity is generally maintained above the
baseline 320. The gradual ramping periods 222 and 223 may
individually or in the aggregate be for a period greater than a
normal intrinsic inspiration period or over a period during a
plurality of breaths. While switched ramping is shown with respect
to electrodes at two different hemidiaphragms, such switched
ramping may be provided with any two or more electrodes or
electrode pairs, whether positioned on the same hemidiaphragm or
not. Switched ramping may be provided with more than two electrodes
or electrode pairs providing overlapping stimulation with different
electrodes or electrode pairs to permit rest of the diaphragm or
nerve associated with an electrode or electrode pair.
[0040] The gradual ramping periods 322 and 323 may be for a period
greater than a normal intrinsic inspiration period or over a period
spanning a plurality of breaths. While a lung volume bias is
illustrated, other stimulation may be ramped up or down in
accordance with an aspect of the invention. This stimulation may be
used to prevent fatigue by resting stimulated portions of the
diaphragm or phrenic nerve while maintaining stimulation on.
[0041] In accordance with one aspect of the invention, stimulation
is provided by varying one or more stimulation parameters, e.g.,
amplitudes, frequencies, pulse widths and/or burst durations or
burst frequencies, stimulation on/off periods, to avoid fatigue or
adaptation. Such stimulation parameters may be within a desired
range or may be altered to provide an optimization of diaphragm
rest and diaphragm activation. Such stimulation protocol may be
generally open loop where a predetermined program or sequence is
used for preset time periods to stimulate and also provide rest.
Stimulation may be cycled through different amplitudes and/or
frequencies. Such stimulation protocol may also be generally closed
loop where stimulation parameters are adjusted based on feedback
indicating rest is needed or that adaptation is occurring.
Stimulation may also be adjusted or cycled on or off depending upon
a patient status, such as, for example, sleep state status, or
other condition or status. Such protocol may be a combination of
open loop and closed loop wherein stimulation is provided for a
period of time according to a protocol and then sensing is used to
periodically determine stimulation and response status. For
example, after a period of stimulation, detection or sensing may be
used to determine if breathing is continuing to be stabilized after
stimulation. Stabilized ventilation may be detected using methods
and devices that determine variations in lung volume, tidal volume,
functional residual capacity, flow, or other respiration parameter.
Examples of detection are described in further detail herein or in
related applications as set forth herein. Upon detection of
stabilized ventilation, stimulation may be cycled off. Stimulation
may be provided again when breathing stabilization has fallen
off.
[0042] In accordance with one aspect of the invention, stimulation
may be individualized on a patient by patient basis by determining
individual patient response to stimulation, that will achieve a
desired result. For example, polysomnography may be used to provide
therapeutic and/or diagnostic data on individual patients by
observing a patient's sleep data and by observing a patient's
response to therapy. Specific types of therapy, combinations of
therapy and/or therapy parameters may be titrated during
polysomnography studies or during an initialization or
reprogramming period after implant. Specific types of stimulation
and/or combinations have been set forth herein and in related
applications as set forth herein. A number of polysomnography
markers may be used to determine effectiveness of stimulation or
combinations of stimulation such as: volume changes, stability of
flow, removal of flow limitation, FRC, volume, arousals, arousals
in response to or due to stimulation, AHI, SaO2 levels.
Polysomnography may be used for decisions or initialization for
bias therapy, therapy where FRC is increased, or for using other
therapies such as paced breathing, breathing control, augmented
breathing, deep inspiration, duty cycle manipulation or others for
exampled as described in co-pending applications set for the
herein.
[0043] In accordance with an aspect of the invention,
initialization, for example, may provide a determination of a
desired therapeutic functional residual capacity or change in
functional residual capacity to be achieved from stimulation.
According to an aspect normal lung volume levels may be determined
such as a normal or non-pathological tidal volume and functional
residual capacities may be determined. Lung volumes may then be
observed prior to respiratory disordered events for example prior
to flow limitations, arousals or apneas occurring. Therapeutic
stimulation may be provided to raise lung volume to a
non-pathological or normal level. Based on initialization data,
lung volume bias therapy or other therapy such as breathing
augmentation or other therapy to maintain minute ventilation above
the critical level may be provided when the critical threshold has
been reached. Minute ventilation may be calculated on a breath by
breath basis, as a running average or over a predetermined period
of time. Thus drops in tidal volume, FRC or minute ventilation may
trigger therapy where no apnea is present.
[0044] In accordance with another aspect of the invention, ranges
of normal and/or out of range parameters may be set based on
initialized data acquisition and analysis.
[0045] In accordance with one aspect of the invention, the change
in lung volume from awake to sleep may be observed and set as a
therapeutic lung volume.
[0046] According to one aspect, using polysomnography data, a
calculation may be made as to when or at what minute ventilation
the patient's SaO2 levels drop below a critical level. Such
critical level may be defined as a level sufficiently before apnea
occurs (Alternatively it may be defined as a level approximately
when apneas occur).
[0047] Also, a maximum lung volume or minute ventilation may be set
for example, where therapy may be turned off. Such maximum level
may be set, for example as a normal lung volume level plus a
percentage of normal lung volume (e.g., tidal volume or FRC).
Alternatively a maximum minute ventilation may be determined and
set as a normal level plus a percentage of such level. Minimum and
maximum SaO.sub.2 levels may also be set. SaO.sub.2 may be observed
in sleep studies and corresponding to other parameters such as
minute ventilation, lung volume and/or FRC. Or during treatment,
such levels may be detected. Thus if with stimulation tidal volume,
minute ventilation, SaO.sub.2 or other physiological parameter
exceeds a desired or safe level, stimulation may be turned off or
adjusted. Also if a normal level of breathing resumes on top of
stimulation, such lung volume or minute ventilation levels may
exceed a desired level and stimulation may be turned off or the
patient weaned off of stimulation. In accordance with one aspect of
the invention a clinical protocol may be defined where different
FRC increases are tested until a satisfactory improvement in
disease state is obtained. Such as reduced respiratory disturbances
or events, improved SaO.sub.2 levels, improved breathing or
improved cardiovascular function.
[0048] According to another aspect an external programming device
may be provided with software that calculates a recommended
therapeutic volume increase based on patient's weight, sex
abdominal and neck diameter and AHI. This may be used as an initial
value which may then be further titrated.
[0049] Detection as well as therapy parameters may be
individualized on a patient by patient basis where patient
stability markers are determined e.g. using polysomnography data
(for device initialization and/or device programming updating).
Stability markers may include parameters or combination of
parameters that are used to create detection criteria for unstable
breathing. For example, polysomnography data may be recorded for a
period of time where normal breathing is occurring. Ranges of
normal variations in respiratory parameters may be defined. A
statistical analysis may be used to determine or define a range of
normal parameters or combinations of parameters. Also, the changes
that occur with the onset of disordered breathing can be quantified
and used to initialize detection criteria, thresholds or
ranges.
[0050] Referring to FIG. 4, a flow diagram illustrates an example
of individualizing stimulation to provide a desired functional
residual capacity or biased lung volume. An initial estimate of an
optimum FRC increase is determined based on patient characteristics
410. Such characteristics for example, may be height, sex, BMI,
breathing pattern (such as a breathing pattern prior to or leading
to an obstruction or other disordered event) or AHI as determined
from sleep study. Another characteristic or pattern that might be
observed is a percent of hypopnea events versus apnea. This
information may be used to tailor treatment, for example by setting
FRC target higher where there are greater numbers of apneas and
lower where there are fewer. Stimulation is then provided to the
diaphragm or phrenic nerve 420 using the therapeutic device. Lung
volume change is then sensed, observed or determined including
change in functional residual capacity 430 either in synchrony with
stimulation or lasting for a period after stimulation. For example,
the change in FRC produced by stimulus may be observed using a belt
with sensors that measure the displacement of the chest and
abdomen. A magnetometer may be used to measure chest wall
displacement, which is correlated with lung volume, or a
measurement of esophageal pressure may be used in order to
determine a change in intrapleural pressure indicative of a lung
volume change. Then it is determined whether the lung volume change
is at a desired level or not 440. If it is not, then the
stimulation is adjusted or titrated 450. This titration (or
stimulation with the device) may also be done for the left and
right hemidiaphragms individually or together in order to achieve
the desired volume change. In addition, stimulation during
initialization or device use that is provided may be unilateral
using either right or left diaphragm alone. If the desired FRC is
achieved, then the patient is observed in sleep in a clinic at home
collecting sensed data including that typically observed during
polysomnography studies 460 using the titrated parameters.
Information may be telecommunicated as well. Then it is determined
whether the therapy achieved a desired clinical result with the
initialized stimulation parameters using the polysomnography data
or sensed data 470. Typically such observations may be air flow,
EEG, abdominal and rib movement, snore sensor, and SaO2 that
determine the occurrence of apnea or hypopnea events (e.g.
apnea/hypopnea index (AHI)), breathing stability, arousals, oxygen
saturation, presence of snoring or any other data that indicates
effectiveness of therapy. A polysomnography study may show criteria
such as improvement in AHI, arousal index and SaO2 saturation
levels. Additionally or alternatively, a sleep study without
applied therapy may be used as a control to determine if the
stimulation using particular parameters or protocols resulted in an
improvement in any of the clinical parameters observed on the
polysomnograph. If the therapy did not achieve the clinical result,
the stimulus is titrated. The titration may be done incrementally
during one or more studies, or it may be adjusted based on
information accumulated from the previous titration. For example,
earlier titrations may provide information concerning the dose
response, or stimulation parameters associated with corresponding
volume change. If the therapy did achieve the desired clinical
result, then the stimulation parameters are set or programmed into
the therapeutic device 480 until the device is reprogrammed. In
accordance with one aspect of this example, minute ventilation or
other respiratory parameters may be observed and used in addition
or as an alternative to using lung volume, for example in step
430.
[0051] During a sleep study prior to device implant, data may be
collected that includes a diaphragm EMG signal. The signal may be
recorded and analyzed during different respiratory states such as
flow limitation, obstruction, reduced central drive, and central
apnea. This analysis may be used to set EMG based thresholds for
detection of these conditions or events. For example, the EMG
envelope may be calculated, and the width of the envelope may be
determined for each of these conditions. Using statistical methods,
thresholds may be determined based on EMG envelope width that
differentiate, for example, flow limitation from obstruction, or
normal breathing from reduced central drive. A diaphragm EMG may be
used to correlate changes in EMG to a specific respiratory
disorder, disturbance or disease on the EMG.
[0052] To reduce arousals due to stimulation, stimulation
parameters may be modified such as stimulation frequency,
stimulation amplitude or stimulation ramping. This may be
implemented, for example at or prior to device implant. Also
stimulation to one or other hemidiaphragm may be adjusted.
[0053] Other information may be used to determine adaptation to
stimulation where the stimulation may be more effective or less
effective, or fatigue where the stimulation is less effective.
Modification of stimulation parameters may provided in response to
such fatigue or adaptation. Such adjustment of parameters may be
provided by monitoring patient response over time or in a device
with continuous or periodic feedback and adjustment of parameters
based on response to stimulation.
[0054] Device initialization may be provided with input from
external or temporary sensors, for example in a polysomnography
study, or where appropriate when the patient is awake. Such device
initialization may also be provided with sensors and/or detection
incorporated into the stimulation device or its peripherals. Also
such device initialization may be provided periodically or on an
ongoing basis during the term of device usage. The device may be
programmed to adjust stimulation parameters or protocol during the
device usage term.
[0055] In addition to sensing EMG, for initialization or detection,
ECG may be sensed, e.g., from the implanted device, and the data
used to initialize the device or provide feedback during device
use. Heart rate variability, Heart rate RR intervals, may be sensed
with sleep data gathered for a night and analyzed for device
initialization or programming or reprogramming.
[0056] An implantable device may match its sleep disordered
breathing detection with an automated sleep scoring system (for
example Morpheus of SleepMed inc. has such an automated scoring
system) may be used to calibrate implant as well.
[0057] Various detection algorithms may also be incorporated into
the device. The device may be programmed to respond with adjustment
of parameters or turning on or off of stimulation based on various
detections. Detection and detection thresholds may be based on data
polysomnography or data gathered in a real time therapy device
[0058] According to one aspect of the invention, an increase in FRC
or a lung volume bias may be used for therapeutic purposes prior to
materialization of an apnea event where breathing instability is
present. Accordingly detection may comprises detecting flow
limitations or unstable breathing that are not at an apnea level
and providing stability, improving gas exchange or ventilation to
avoid apnea. The device may also detect an imminent apnea event or
onset of an apnea event. If a central or obstructive apnea does
occur, the device may either turn off stimulation, or provide
stimulation according to a different protocol. The device may also
detect an apnea event or events that may indicate possibility of
subsequent events occurring and may turn on stimulation after an
apnea event has resolved.
[0059] Table I is a chart illustrating examples of conditions that
may be detected to trigger a therapy. Detection of one or more
conditions may indicate a respiratory disturbance and/or an
imminent disordered event occurring. It is believed in accordance
with the invention that a variety of diseases, disorder or
conditions can be treated or prevented using one or more
stimulation therapies including those described herein and in
related applications as set forth herein. It is also believed that
therapies that stabilize breathing, assist in maintaining
respiratory drive at a desired level and/or reducing flow
limitations helps reduce arousals prevent onset of respiratory
events such as Cheyne Stokes Respiration or one or more types of
apnea.
[0060] According to one aspect, one or more respiratory
disturbances or indicators is detected and a first treatment is
provided in response. Onset of a disordered breathing event such as
an apnea may be detected, then a second treatment protocol may be
implemented or the first treatment may be modified. Alternatively,
occurrence of a disordered breathing event such as an apnea may be
detected then a second treatment protocol may be implemented or the
first treatment may be modified.
[0061] While not intending to be limiting, Table I provides an
examples of indicators that may be detected. These indicators may
be detected, for example, by sensing one or more respiration
parameters as described herein or in one or more related patent
applications as set forth herein.
TABLE-US-00001 Conditions to Detect Conditions that Indicate
Respiratory Disturbance Possible Indicators of Condition
Instability of Breathing Greater than normal variation of breathing
rate, TV, or FRC Reduction in Central Reduced diaphragm EMG (i.e.
area under Drive the "envelope") Flow Limitation Increased
amplitude, width and frequency content of diaphragm EMG; change,
e.g., flattening of morphology Previous Central or Recent events:
EMG below threshold for Obstructive Apnea breath detection,
amplitude, width and Events frequency content of diaphragm EMG over
threshold for obstructive apnea Imminent Disordered Event Sleep
data to identify indicators of imminent disordered event including
respiratory parameters, blood gas levels or other physiological
parameters identified from sleep data observation Airway
obstruction (or Further increase amplitude, width and Disordered
Event Onset) frequency content of diaphragm EMG, over that of flow
limitation Central apnea(or EMG amplitude that is below threshold
for Disordered Event Onset) breath detection.
[0062] Detecting unstable breathing and providing stimulation such
as, for example, bias, augmentation, paced breathing or breathing
control may treat one or more diseases, disorders of conditions
associated with unstable breathing and may prevent disordered
breathing events. Unstable breathing may be detected by sensing a
greater than normal variation in one or more respiratory
parameters. It also may be detected for example by sensing snoring,
for example as described in more detail herein. Patterns of
breathing instability may be observed. For example if breathing
instability occurs through out the night or increases, then
stimulation may be provided or tailored to that pattern to reduce
the occurrence of unstable breathing or related events.
[0063] Detecting a reduction in central drive and providing
stimulation such as bias may prevent an obstructive event that can
occur during or following a reduction in central drive. Also
augmenting breathing or pacing breathing may be used to treat a
reduction in central drive. Reduction in central drive may be
detected by observing drops in tidal volume or slope of tidal
volume waveform or one or more parameters of the EMG complex. In
accordance with one aspect an average tidal volume over a period of
time may be calculated. A threshold may be determined based on that
average below which a drop in tidal volume or a drop in flow is
detected. The tidal volume or current flow will be compared to that
threshold. If it is less than the threshold, then a reduction in
central drive is detected. Detection occurs when a drop in tidal
volume or flow occurs. This allows the start of stimulation before
onset of an obstructive episode or central episode.
[0064] Detecting a flow limitation and providing stimulation such
as described herein may be used to reduce flow limitations and
possible sleep disordered events. A flow or EMG template may be
recorded during flow limitation at initialization. Then during
device operation the current flow or one or more parameters of an
EMG waveform may be compared to the template. If there is a close
enough match to the template then a flow limitation is detected.
Additionally, flow limitation may worsen over time. A threshold may
be set based on the degree of limitation and number of flow
limitation episodes that are observed.
[0065] Detection of the occurrence of a previous disordered events
may be used to trigger therapy or to prevent subsequent events. For
example after an event or pattern of events have occurred,
stimulation may be turned on to increase functional residual
capacity to reduce the likelihood of further events occurring.
Other stimulation may also be triggered as well, by detecting
events that have occurred. There may be a threshold set such that a
certain number of events must occur before therapy is
delivered.
[0066] Detecting the imminent onset of a disordered event may
trigger therapy such as bias therapy to prevent the event from
occurring. Bias therapy may reduce instability, improve gas
exchange while permitting intrinsic breathing to continue. Sleep
data to identify indicators of imminent disordered event may
include changes in respiratory parameters such as in flow, tidal
volume, FRC, blood gas levels, certain slope of drop in tidal
volume, or other physiological parameter changes that occur
immediately prior to an obstructive event. Patterns of change or
values of such parameters, identified from sleep data observation
may be stored as data. Then parameters from one or more breaths may
be observed and analyzed, searching for a repetition of the
pattern.
[0067] A further increase in amplitude, width and/or frequency
content of diaphragm EMG, over that of flow limitation may be used
to detect an obstructive event. Recordings of a known EMG during
obstruction may also be used as a template for comparison to a
current template to detect and obstructive event. For example, if
more than a certain number of parameters of the template similar
within a given percent margin, then OSA will be detected.
[0068] If an EMG amplitude is below a threshold for breath
detection, a central event may be detected. Stimulation may be
turned off to prevent obstructions, or paced breathing may be
provided.
[0069] FIG. 5A is a flow chart illustrating detection and treatment
using a device or method in accordance with one aspect of the
invention. One or more respiration parameters are monitored 510.
One or more conditions are detected indicating a respiratory
disturbance 515. Therapy is turned on to increase FRC or to create
a lung volume bias 520. One or more respiration parameters are then
monitored 525 to determine if respiration is stable 530. If
respiration is not stable, the lung volume bias or therapy to
increase FRC is adjusted according to a protocol 535. If
respiration is stable then after respiration has been stable for a
predetermined period of time 540, therapy is turned off of the
patient is weaned off of therapy 545. If respiration is not stable
for the predetermined period of time 540 then the respiration
parameter is monitored again to detect stable respiration 525 and
530.
[0070] In accordance with another aspect of the invention as
illustrated in FIG. 5B, a second detection may be added to the
detection and treatment of FIG. 5A. If the second detection is
added, then at step 535 if respiration is not stable and if a
second condition is detected indicating an onset or an imminent or
present respiratory disordered event or if a determination is made
that previous therapy is not leading to respiratory stability 546,
then therapy is adjusted or a second therapy is provided 550. One
example of such adjustment may be, for example, if flow limitation
still is detected after bias stimulation, stimulation may be
switched to a stimulation protocol to increase inspiration
duration.
[0071] One or more respiratory parameters are monitored 555. If
respiration has not stabilized 560 then therapy is adjusted
according to a protocol 565 and respiration is monitored again at
step 555. If respiration is stable then if respiration has been
stable for a preset period of time 570 therapy is turned off of the
patient is weaned from the therapy 575 respiration is then
monitored again at step 510 (FIG. 5A). If respiration has not been
stable for a preset period of time 570 then therapy is returned to
step 555. An example of a second therapy may be paced breathing if
a central apnea is detected or a turn off of therapy if an
obstruction is detected. The step of detecting if a second
condition is present may also determine such second condition from
one or more types of conditions. For example detecting the second
condition may detect obstructive apnea or central apnea and
determine which type of apnea is occurring or has occurred. If at
step 546 a second condition is not detected indicating an onset or
an imminent or present respiratory disordered event and if a
determination is not made that previous therapy is not leading to
respiratory stability, then return to step 525
[0072] FIG. 5C is a flow chart illustrating detection and treatment
for upper airway flow limitation or obstruction. Detection
parameters are initialized 580, e.g., in a manner as set forth
herein. The EMG complex is processed and monitored 581 to determine
if a flow limitation threshold has been crossed 582, for example,
as described in more detail with respect to FIGS. 6A-6E herein. If
the threshold for flow limitation has not been crossed then
monitoring continues at step 581. If the threshold for flow
limitation has been crossed 582, then it is determined whether the
flow limitation has also crossed the threshold for airway
obstruction 583. If there is an airway obstruction, then the
therapy is turned on, turned off or adjusted according to a
protocol where appropriate 584 until the end of the obstruction 585
after which monitoring resumes at step 581. If at step 583, a
threshold has not been crossed for airway obstruction then the
appropriate therapy is turned on and a timer is set 586. The EMG
complex is then monitored and processed 587. It is then determined
if the response to the therapy is acceptable 588. If it is not,
then therapy is adjusted 589 and monitoring continues at step 587.
If the response to the therapy is acceptable at step 588, then if a
timeout (preset time period) has not been reached 590 monitoring
continues at step 587. If the response to the therapy is acceptable
at step 588 and a timeout has been reached at step 590, then the
patient is weaned off of the therapy 591 and monitoring begins
again at step 581.
[0073] In addition to using detection of respiratory instability,
respiratory disorders or imminent onset of a respiratory disorder
to trigger therapy, therapy may be triggered after an event (or a
number of events) has occurred such as an obstructive or central
event. According to an embodiment, detection of an arousal may
trigger delayed turning on of bias stimulation. Bias stimulation
may then be turned on for a period of time. An occurrence of an
event or events may indicate that a patient is more susceptible to
additional events occurring and a therapy such as a bias therapy
may be turned on for a predetermined period of time. A number of
physiological conditions may increase likelihood of events such as
onset of sleep or a particular sleep state. Detection of such
events may also be used to trigger therapy where the events are
known to increase a patient's susceptibility to apneas or other
respiratory disorders.
[0074] A patient's episode patterns may be observed and therapy
type or combinations of therapies may be selected. During
polysomnography study for device initialization, a number of
different therapies or combination may be evaluated or titrated
based on observed patterns before or resulting from tested or trial
therapy. If, for example, there is a tendency for central or mixed
apneas, detection or therapy may be keyed to specific patient
pattern. A type of therapy for a particular pattern may be
selected, for example if the event is primarily central, a
particular therapy may be selected; if the event starts as an
obstructive event and then continues as a central event another
therapy may be selected. For example, if a patient has a tendency
to have events that are obstructive or flow limited followed by
mixed events, bias therapy may be turned on at an early indication
of breathing instability, to stabilize breathing by improving
stability of the upper airway or of flow. In a patient with
disordered breathing that tends to be initially centrally mediated,
bias may be turned on prior to an event, followed by stimulation
during breathing to augment breathing or paced breathing to treat
the centrally mediated disorder.
[0075] In a closed loop system, it may be desirable to avoid
turning on during periods of severe flow limitation as stimulation
during such periods may not be as efficient particularly where
severe airway resistance reduces the ability of stimulation to
increase functional residual capacity. Timing of bias may be
synchronized with respiration so that it provides a more efficient
increase in functional residual capacity (as the airway is already
opening and breathing is occurring).
[0076] In addition to detection set forth above, as a safety
mechanism, the device may be provided with sensors that confirm
that breathing is occurring on top of bias stimulation
[0077] In accordance with another aspect of the invention, sensing
may be provided of external or environmental conditions for example
atmospheric pressure changes due to change in altitude. Stimulation
or detection may be adjusted base on such external or environmental
characteristics.
[0078] In accordance with one aspect of the invention, a plurality
of thresholds are used to determine a plurality of levels of airway
obstruction or flow limitation.
[0079] Detection of thresholds for flow limitation and complete
obstruction in accordance with the invention may be determined
related to the effort or magnitude of effort. As effort increases,
a number of features in the EMG complex change. EMG envelope has
been used to determine effort. The EMG envelop is obtained using an
averaging process. However the EMG envelope determination process
does not take into account all of the different magnitude changes
that occur in an EMG complex with an increase in effort. Such
factors include the frequency content changes, the width of the
complex increase, increase in rising slope of EMG envelope and the
increase in amplitudes and density of the individual spikes. In
accordance with one aspect of the invention, an improved detection
of effort is provided which takes into account one or more of the
factors of the EMG complex. In accordance with another aspect of
the invention in order to obtain a more accurate determination of
effort, a plurality of factors of the EMG complex are used to
determine degree of obstruction or flow limitation. For example, a
power spectral density plot of EMG may be used to determine effort.
Also frequency content of an EMG may be used to determine effort.
Because frequency content increases with increased effort, the area
under the Power Spectral Density Plot, e.g., between 100 and 500 Hz
increases for flow limited activation (breath) versus non flow
limited activation. A threshold may be set corresponding to an area
under the PSD for detecting flow limitation or obstruction.
[0080] Referring to FIGS. 6A, 6B and 6C, EMG, EMG envelope and
tidal volume are illustrated under different levels of flow
limitation. The diaphragm EMG as well as upper airway (genioglossal
EMG and intercostals show an increased activity with increased
breathing effort. The increased activity can be measured through
processing of the diaphragm EMG or EMG from other respiratory
muscles to obtain an EMG envelope for each phasic activity. The
envelope can be created by rectifying the signal, performing a
window average over about 100 ms performing peak detection to
obtain an envelope amplitude, and an integration of the area under
the averaged signal to produce an envelope area. This processing to
obtain an EMG envelope is generally known in the art. In accordance
with one aspect, the phase of the diaphragm EMG with respect to
other respiratory muscles may indicate obstruction or flow
limitation. In accordance with one aspect of the invention, the EMG
envelop may be used to differentiate between flow limitation and a
greater level of obstruction. Where there is a flow limitation or
flow obstruction, effort increases as does the EMG envelope
amplitude. In addition as effort increases, e.g. due to greater
limited flow or increased flow resistance, a number of features in
the EMG complex change. The frequency content increases, the
amplitude of the EMG spikes increases, the rising slope of the EMG
complex increases and the width of the complex increases and the
area under the envelope increases. One or more of the parameters
may be used to identify when there is a flow limitation or when
there is a flow obstruction. One or more thresholds may be set to
determine one or more of these conditions.
[0081] Breaths 601, 602, 603, 604 show a normal EMG with a normal
EMG envelope and a normal tidal volume. Breath 605 shows an
increased EMG envelope (FIG. 6B), a reduced tidal volume and an EMG
complex (FIG. 6A) with higher amplitude and components of increased
frequency, indicating a flow limitation. Breaths 606, 607, 608 and
609 show a further increased EMG envelope (FIG. 6B), a further
reduced tidal volume and a EMG complex (FIG. 6A) with even higher
amplitude and components of increased frequency, indicating a flow
obstruction. As shown in FIG. 6E the EMG envelope for a flow
limited breath is greater in amplitude and duration for a flow
limited breath 650 as compared to those of a normal breath 640. The
EMG envelope for a flow obstructed breath 660 is greater in
amplitude and duration than the EMG for a lower level flow limited
breath 650. Thus using an EMG envelope, the increase in the
envelope can be sensed or determined and used to determine when a
flow limitation is occurring at a first threshold, and where an
obstruction is occurring at a second threshold. The thresholds may
be determined on a patient by patient basis. The thresholds may
also distinguish degrees of flow limitation as well as flow
limitation being distinguished from an obstruction, or either being
distinguished form a normal breath.
[0082] As shown in FIG. 6D a Power Spectral Density (PSD) plot is
illustrated of an EMG complex of a normal breath 610, of an EMG
complex of a flow limited breath 620 and an EMG complex of an
obstructed breath 630. As can be seen, there is an increase power
density of higher frequency components of the EMG as obstruction
occurs to a greater degree. The area under the PSD curve within a
particular frequency range may be used to determine normal
breathing versus flow limited breathing versus upper airway
obstruction. Because the frequency content increases with increased
effort, the area under the Power Spectral Density Plot between 100
Hz and 500 Hz (or the PSD in that bandwidth) increases as flow
limitation increases. Thus using an EMG signal, the increase in
frequency content of the complexes can be sensed or determined and
used to determine when a flow limitation is occurring at a first
threshold, and where an obstruction is occurring at a second
threshold. The thresholds may be determined on a patient by patient
basis. The thresholds may also distinguish degrees of flow
limitation as well as flow limitation being distinguished from an
obstruction or either being distinguished form a normal breath.
[0083] FIGS. 7A-7C illustrate use of a device and method whereby a
bias stimulation is provided for a period over more than one breath
and preferably several breaths.
[0084] According to another aspect of the invention, the
stimulation is cycled off (or on) at a preselected portion of a
respiration cycle. FIGS. 7A-7C further illustrate use of a device
and method whereby a bias stimulation is provided and then is
turned off to create a therapeutic benefit. Bias stimulation 750
(FIG. 7C) is provided to thereby increase functional residual
capacity from a baseline 720 to an increased biased level 730 (FIG.
7B). Stimulation is turned off at the end of inspiration or the
beginning of exhalation which provides an increased negative flow
710 (FIG. 7A), and increased positive pressure in the upper airway
during exhalation. In accordance with one aspect of the invention,
bias is cycled off to provide an increase in upper airway
patency.
[0085] FIGS. 8A-8C illustrate different levels of increased FRC
(e.g. from a reference point) achieved by different levels of low
level bias stimulation. As can be seen low level bias stimulation
can increase FRC in different amounts to achieve a desired
therapeutic effect. In FIG. 8A a baseline FRC 810 is at about 3
Liters of volume above a residual lung volume 805. Stimulation is
turned on at point 815. Stimulation is provided where functional
residual capacity 820 is increased to about 3.5 liters, e.g., the
FRC change is below the tidal volume 822 of a normal intrinsic
breath 821. The FRC is increased by about 0.5 liter or 1/2 of a
tidal volume of about 1 liter. In FIG. 8B a baseline FRC 830 is at
about 3 Liters of volume above a residual lung volume 825.
Stimulation is turned on at point 835. Stimulation is provided
where functional residual capacity 840 is increased to about 4
liters, e.g., approximately at the tidal volume 842 of a normal
intrinsic breath 841. The FRC is increased by about 1 liter or
about the same as tidal volume of about 1 liter. In FIG. 8C a
baseline FRC 850 is at about 3 Liters of volume above a residual
lung volume 845. Stimulation is turned on at point 855. Stimulation
is provided where functional residual capacity 860 is increased to
about 4.5 liters, e.g., the FRC increase is above the tidal volume
862 of a normal intrinsic breath 861. The FRC is increased by about
1.5 liter or 11/2 times a tidal volume of about 1 liter.
[0086] FIG. 9A illustrates a normal flow (FIG. 9A), a normal EMG
envelope (FIG. 9B) and normal lung volume (FIG. 9C) at breaths 901,
902 where there is no stimulation (FIG. 9D). Flow is decreasing
(FIG. 9A) along with EMG envelope (FIG. 9B) and tidal volume (FIG.
9C) at breaths 903, 904, 905. Reduced flow, EMG and/or lung volume
may be detected and may trigger a first stimulation therapy. A low
level or bias stimulation 920 (FIG. 9D) is then provided during
breaths 906, 907, 908, 909 which results in an increase in
functional residual capacity 931 from baseline 930. This increase
in functional residual capacity may be therapeutic and may result
in resumption of improved drive or breathing from improved gas
exchange and/or increased upper airway stability due to an
increased functional residual capacity. After breath 909, a central
apnea event occurs. While bias stimulation 920 continues, a paced
breath is stimulated 921 to elicit breath 910. Providing bias
stimulation before paced breathing or continued during paced
breathing may further stabilize the airway during paced breathing.
Such paced breathing may continue for a period of time.
[0087] Bias stimulation provided before during and/or after other
diaphragm stimulation such as breathing control stimulation,
augmentation, duty cycle control, paced breathing or other
stimulation, for example, as disclosed in co-pending related patent
applications set forth herein. Such bias stimulation may reduce a
possibility of upper airway closure during the other
stimulation.
[0088] Bias stimulation may be used in combination with paced
breathing or other diaphragm stimulation of respiration, to
stabilize the upper airway, and avoid obstructions or the need for
tracheotomies in patients who have diaphragm stimulators. For
example bias may be used in a diaphragm stimulation device with
paralysis patients, ALS patients or other patients who would
otherwise need chronic ventilator support.
[0089] According to another aspect of the invention a motion sensor
or position sensor may be used to determine a patient's position
and adjust the stimulation accordingly. For example, therapy may be
turned on for a patient with an obstructive disorder where the
patient's events are position sensitive. For example the therapy
may be turned on when the patient is supine, and the therapy may be
turned off when a patient rolls on their side. The stimulation
intensity or other parameter may be adjusted depending on a
patient's position. The change in position may lead to a change in
FRC. Stimulation may be adjusted based on a change in position or a
change in FRC. There is also typically a fall in FRC when the
patient's state changes from awake to sleep. If this volume change
is measured for a patient, it may be used to target a therapeutic
volume. For example, the therapeutic volume increase is the same as
the FRC fall when the patient goes to sleep.
[0090] In accordance with one aspect of the invention, diaphragm
stimulation may be combined with Autonomic Nervous System (ANS) or
vagal or other parasympathetic activation. In accordance with
another aspect of the invention a device for treating apnea having
either a component of OSA or CSA by stimulating the diaphragm or
phrenic nerve to elicit a diaphragm response, is combined with a
vagal stimulation (or other parasympathetic activation caused by
electrical stimulation.) For example, diaphragm/phrenic stimulation
may cause an increased FRC or biased lung volume, or may modify or
control breathing. Neural stimulation to the ANS may also be
provided to have an excitatory effect on respiratory drive. Such
stimulation may be directly to the central nervous system or to
afferents to the central nervous system. Stimulation to one or the
other (diaphragm/phrenic or ANS) may be done simultaneously or in
an alternating manner. A fully implantable device with multiple
leads may be used or external devices may be used or a combination
of both. The advantage of combining two types of stimulation, for
example, may be that the phrenic nerve stimulation may treat the
obstruction or flow limitation by eliciting a mechanical increase
in lung volume while the parasympathetic stimulation may help
reduce or control sympathetic activation or sympathetic bias that
occurs during apnea, to reduce or avoid sharp changes in blood
pressure and/or overshooting of respiratory drive that can occur
following an apnea.
[0091] FIGS. 10A to 10C illustrate an example of an unstable
breathing detector and treatment device in accordance with an
aspect of the invention. FIG. 10A schematically illustrates output
of an audio sensor configured to sense noise or sound associated
with snoring. Snoring indicates some degree of airway obstruction
and may be correlated to flow limitation. In the example
illustrated, as level of snoring increases at breaths 1023, 1024,
1025, a decrease in tidal volume is associated with the snoring
(FIG. 10B). Snoring may decrease again (breaths 1026, 1027) and
then increase again (breaths 1028, 1029) illustrating instability
in breathing and fluctuations in flow and tidal volume. A bias
stimulation 1050 is provided at 1040 which provides a decrease
(breaths 1030, 1031) in snoring and a normalization or
stabilization of an intrinsic normal tidal volume where snoring
falls below a detectable level (breaths 1032, 1033, 1034).
[0092] FIGS. 10A-10C schematically illustrate an effect of
stimulation on unstable breathing. While a sensor such as an audio
sensor is illustrated. The treatment may alternatively be provided
without sensory feedback or with limited sensor feedback for
example that indicates an appropriate time for turning on or off
therapy for a predetermined period of time or according to a
predetermined protocol.
[0093] Additionally, while FIGS. 10A-10C illustrate the use of
snoring and treatment of snoring as well as treatment of unstable
breathing. Other types or forms of unstable breathing or other
indications of unstable breathing may be used to identify the
presence of unstable breathing. For example, unstable breathing may
include an above normal variability in flow, lung volume, tidal
volume, breathing rate, minute ventilation, blood gas levels. Such
examples may include, those set forth herein and in related
applications as set forth herein.
[0094] Stimulation in the various embodiments described herein may
be patient or clinician activated. For example, a patient may turn
a device on before going to sleep. The device may turn on therapy a
predetermined time after the patient has turned the device on. The
patient may also be provided with an actuation device that delays
stimulation when desired, for example for a predetermined period of
time. A device may also include sensors or algorithms that turn the
device on or off for periods of time, for example during sleep or a
particular sleep stage. The device may then provide stimulation
according to a predetermined program, for example, intermittently
during sleep. Such device may be open loop in that it does not
necessarily respond to particular respiratory events. The device
may be closed loop in that it senses respiration or other
physiological parameters after it has been turned on to respond or
adjust based on the parameters. Examples of closed loop detection
may include those set forth herein and in related applications as
set forth herein.
[0095] Stimulation may be triggered on or off by a user or
provider, by detection of a patient sleep state. The device may be
turned on or off in a number of manners including, e.g., patient
turn on followed by delay; patient turn on and an immediate start;
turn on based on time of day; turn on or off based on awake/sleep
state; or by detection of an event (either onset or resolution).
The device may also be turned off upon detection of patient waking
up or patient manual deactivation.
[0096] The device may be turned on or off, or therapy triggered
upon detection of sleep or sleep state. Sleep leads to a number of
changes in the body's autonomic function, and physiological
parameters. A number of these changes can be detected by the
implanted device or external sensors. Activity level can be
detected with an implanted or externally attached accelerometer,
where a decreased activity can be indicative of sleep. Also, a
multidimensional accelerometer can be used to detect that the
patient is in a sleep or resting position and turn on/off therapy,
or put the device into a "waiting state" for detection of breathing
disordered events. In addition, changes in respiratory parameters
such as breathing rate, and minute ventilation can be used to
detect sleep. For example, baseline respiration rate and minute
ventilation can be determined when the patient is in known states,
i.e. quiet resting versus sleep. This information could be used to
help the device to discriminate between those states. Also the
synchrony of respiration with cardiac rhythm changes when going
from the wake to the sleep state. This would require a learning
algorithm where the device would learn through recording of
baseline data the typical synchrony of the respiration versus the
heart rate during sleep, and use this information in a sleep
detection algorithm. The cardiac rhythm alone can be used to detect
sleep as well. For example, histograms could be created for heart
rate and heart rate variability in the sleeping and waking state,
and these histograms could be used to create reasonable thresholds
to allow differentiation between sleep and wake, based on heart
rate or heart rate variability.
[0097] In addition to individual parameters, the criteria for sleep
detection may be a combination of a number of factors, for instance
patient indicating that he is laying down and preparing for sleep,
time of day, heart and respiratory rate or pattern. When two or
more of the criteria are met the device may determine that the
patient was asleep.
[0098] In addition to differentiating between in sleep and awake
state, the device may differentiate between different stages of
sleep. The stages of sleep include Stage 1, a transitional stage,
Stage 2, a light sleep state, Stage 3 and 4, slow wave or deep
sleep, and REM, or rapid eye movement sleep, where dreaming, muscle
paralysis, and a lot of variability in sympathetic tone occur.
Patients vary according to which sleep stage most of their
disordered breathing occurs. But in most patients, REM sleep is
where a majority of OSA episodes occur due to the reduced
functioning of the upper airway muscles, and stage 3 and 4 are
relatively free of breathing disordered events. Therefore it may be
advantageous for the device to turn on or adjust therapy to a
higher level at the detection of REM sleep, and turn off or reduce
therapy at detection of stage 3 and 4 sleep.
[0099] While the invention has been described in detail with
reference to preferred embodiments thereof, it will be apparent to
one skilled in the art that various changes can be made, and
equivalents employed, without departing from the scope of the
invention.
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