U.S. patent application number 11/690065 was filed with the patent office on 2007-12-06 for systems and methods for modulating autonomic function.
This patent application is currently assigned to Advanced Circulatory Systems, Inc.. Invention is credited to Keith G. Lurie.
Application Number | 20070277826 11/690065 |
Document ID | / |
Family ID | 46300744 |
Filed Date | 2007-12-06 |
United States Patent
Application |
20070277826 |
Kind Code |
A1 |
Lurie; Keith G. |
December 6, 2007 |
SYSTEMS AND METHODS FOR MODULATING AUTONOMIC FUNCTION
Abstract
In one embodiment, a method for modulating a person's autonomic
function comprises interfacing a valve system to the person's
airway, the valve system being configured to decrease or prevent
respiratory gas flow to the person's lungs during at least a
portion of an inhalation event. The person is permitted to inhale
and exhale through the valve system, wherein during inhalation the
valve system functions to produce a vacuum within the thorax to
transiently decrease intrathoracic pressure and thereby modulate
the person's autonomic function.
Inventors: |
Lurie; Keith G.;
(Minneapolis, MN) |
Correspondence
Address: |
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER
EIGHTH FLOOR
SAN FRANCISCO
CA
94111-3834
US
|
Assignee: |
Advanced Circulatory Systems,
Inc.
Eden Prairie
MN
55344
|
Family ID: |
46300744 |
Appl. No.: |
11/690065 |
Filed: |
March 22, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10765318 |
Jan 26, 2004 |
7195013 |
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11690065 |
Mar 22, 2007 |
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10660462 |
Sep 11, 2003 |
7082945 |
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10765318 |
Jan 26, 2004 |
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10460558 |
Jun 11, 2003 |
7185649 |
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10660462 |
Sep 11, 2003 |
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10426161 |
Apr 28, 2003 |
7195012 |
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10460558 |
Jun 11, 2003 |
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10401493 |
Mar 28, 2003 |
7204251 |
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11690065 |
Mar 22, 2007 |
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10224263 |
Aug 19, 2002 |
6986349 |
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10401493 |
Mar 28, 2003 |
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10119203 |
Apr 8, 2002 |
7210480 |
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10224263 |
Aug 19, 2002 |
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09854238 |
May 11, 2001 |
6604523 |
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10119203 |
Apr 8, 2002 |
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09546252 |
Apr 10, 2000 |
6526973 |
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09854238 |
May 11, 2001 |
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08950702 |
Oct 15, 1997 |
6062219 |
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09546252 |
Apr 10, 2000 |
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08149204 |
Nov 9, 1993 |
5551420 |
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08950702 |
Oct 15, 1997 |
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Current U.S.
Class: |
128/205.24 |
Current CPC
Class: |
A61M 16/202 20140204;
A61M 2016/0027 20130101; A61M 2230/205 20130101; A61H 2201/5007
20130101; A61M 2230/432 20130101; A61M 16/107 20140204; A61H 31/00
20130101; A61M 16/0084 20140204; A61M 2016/0021 20130101; A61M
16/208 20130101; A61M 16/20 20130101; A61M 2230/42 20130101; A61M
2230/208 20130101; A61M 16/024 20170801; A61M 16/06 20130101; A61M
2230/06 20130101; A61M 2230/30 20130101; A61H 31/006 20130101; A61M
16/0009 20140204; A61M 2230/50 20130101; A61M 16/0825 20140204;
A61M 2016/0036 20130101; A61M 16/0078 20130101 |
Class at
Publication: |
128/205.24 |
International
Class: |
A62B 9/02 20060101
A62B009/02 |
Claims
1-22. (canceled)
23. A method for altering a person's intracranial pressure to
thereby modulate the person's autonomic tone, the method
comprising: interfacing a valve system to the person's airway, the
valve system being configured to decrease or prevent respiratory
gas flow to the person's lungs during at least a portion of an
inhalation event; permitting the person to inhale and exhale
through the valve system, wherein during inhalation the valve
system functions to produce a vacuum within the thorax to
transiently decrease intrathoracic pressure, decrease intracranial
pressure and thereby modulate the person's autonomic tone; wherein
the valve system includes a pressure responsive inflow valve, and
further comprising setting an actuating pressure of the valve to be
in the range from about -2 cm H2O to about -30 cm H2O.
24. A method as in claim 23, further comprising setting the
actuating pressure of the valve to be in the range from about -3 cm
H2O to about -12 cm H2O for flow rates between about 30 to about 50
liters per minute.
25. A method as in claim 23, wherein during inhalation the valve
system functions to decrease the person's heart rate and peripheral
vascular tone.
26. A method as in claim 23, wherein during inhalation the valve
system functions to increase blood flow back to the right heart of
the person, thereby enhancing vital organ perfusion and
function.
27. A method as in claim 23, wherein during inhalation the valve
system functions to increase heart rate variability.
28. A method as in claim 23, wherein during inhalation the valve
system functions to reduce the person's anxiety level.
29. A method as in claim 23, wherein during inhalation the valve
system functions to treat shock secondary to hypovolemia, sepsis
and heart failure.
30. A method as in claim 23, wherein during inhalation the valve
system functions to treat states of hypo-perfusion that are
selected from a group consisting of wound healing, stroke and
diseases where blood flow is compromised, wherein at least one of
the diseases comprises coronary artery disease.
31. A method as in claim 23, wherein during inhalation the valve
system functions to improve blood flow to the muscles and brain,
thereby reducing heart rate and enhancing recovery from physical
exertion.
32. A method as in claim 23, wherein the valve system is
incorporated into a facial mask or a mouthpiece, and further
comprising coupling the facial mask or the mouthpiece to the
person's face.
33. A method as in claim 23, further comprising coupling at least
one physiological sensor to the patient to monitor at least one
physiological parameter of the person while breathing through the
valve system, and varying the actuating pressure based on the
monitored physiological parameter.
34. A method for repetitively increasing a person's sympathetic
tone to prevent hypotension, the method comprising: interfacing a
valve system to the person's airway, the valve system being
configured to decrease or prevent respiratory gas flow to the
person's lungs during at least a portion of an inhalation event;
permitting the person to inhale and exhale through the valve
system, wherein during inhalation the valve system functions to
produce a vacuum within the thorax to improve blood flow to the
muscles and brain, and to increase the person's sympathetic tone to
prevent hypotension; wherein the valve system includes a pressure
responsive inflow valve, and further comprising setting an
actuating pressure of the valve to be in the range from about -2 cm
H2O to
35. A method for repetitively increasing a person's sympathetic
tone to prevent hypotension, the method comprising: interfacing a
valve system to the person's airway, the valve system being
configured to decrease or prevent respiratory gas flow to the
person's lungs during at least a portion of an inhalation event;
permitting the person to inhale and exhale through the valve
system, wherein during inhalation the valve system functions to
produce a vacuum within the thorax to improve blood flow to the
muscles and brain, and to increase the person's sympathetic tone to
prevent hypotension; wherein the valve system includes a pressure
responsive inflow valve, and further comprising setting an
actuating pressure of the valve to be in the range from about -2 cm
H2O to about -30 cm H2O; and measuring one or more physiological
parameters before and after a period of inhalation through the
valve system to thereby evaluate the patient's condition based on a
change of such measured parameters.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation in part application of
U.S. application Ser. No. 10/660,462, filed Sep. 11, 2003, which is
a continuation in part application of U.S. patent application Ser.
No. 10/460,558, filed Jun. 11, 2003, which is a
continuation-in-part of U.S. patent application Ser. No.
10/426,161, filed Apr. 28, 2003, the complete disclosures of which
are herein incorporated by reference.
[0002] This application is also a continuation in part application
of U.S. patent application Ser. No. 10/401,493, filed Mar. 28,
2003, which is a continuation in part application of U.S. patent
application Ser. No. 10/224,263, filed Aug. 19, 2002, which is a
continuation in part application of U.S. patent application Ser.
No. 10/119,203, filed Apr. 8, 2002, which is a continuation in part
application of U.S. patent application Ser. No. 09/854,238, filed
May 11, 2001, which is a continuation in part application of U.S.
patent application Ser. No. 09/546,252, filed Apr. 10, 2000, which
is a continuation of U.S. patent application Ser. No. 08/950,702,
filed Oct. 15, 1997 (now U.S. Pat. No. 6,062,219), which is a
continuation-in-part application of U.S. patent application Ser.
No. 08/403,009, filed Mar. 10, 1995 (now U.S. Pat. No. 5,692,498),
which is a continuation-in-part application of U.S. patent
application Ser. No. 08/149,204, filed Nov. 9, 1993 (now U.S. Pat.
No. 5,551,420), the disclosures of which are herein incorporated by
reference.
BACKGROUND OF THE INVENTION
[0003] This invention relates generally to the field of
intrathoracic pressures. More specifically, the invention relates
to a variety of conditions that may be treated by manipulating
intrathoracic pressures.
[0004] A widespread need exists for treating ailments associated
with poor blood flow and low blood pressure. For instance, poor
blow flow and low blood pressure may be linked to conditions such
as poor wound healing, strokes, heart failure, anxiety disorders,
sleep disorders and the like. Hence, this invention is related to
the intentional manipulation of internal body pressures in order to
treat these and a variety of other conditions.
BRIEF SUMMARY OF THE INVENTION
[0005] In one embodiment, the invention provides a method for
modulating a person's autonomic function. According to the method,
a valve system is interfaced to the person's airway. The valve
system is configured to decrease or prevent respiratory gas flow to
the person's lungs during at least a portion of an inhalation
event. The person is permitted to inhale and exhale through the
valve system. During inhalation the valve system functions to
produce a vacuum within the thorax to transiently decrease
intrathoracic pressure and thereby modulate the person's autonomic
function. More specifically, by lowering the intrathoracic
pressure, the person experiences enhanced venous return of blood to
the heart, and this causes an increase in cardiac output, an
increase in blood pressure, and increase in blood flow to the
brain, a decrease in intracranial pressure, and an autonomic
nervous system-modulated decrease in sympathetic tone resulting in
a decrease in peripheral arterial resistance.
[0006] For such a treatment, the valve system may include a
pressure responsive inflow valve having an actuating pressure of
the valve in the range from about -2 cm H2O to about -30 cm H2O,
and more preferably from about -3 cm H2O to about -12 cm H2O for
flow rates of about 30 to about 50 liters per minute. In such
cases, inhalation the valve system may function to decrease the
person's heart rate and peripheral vascular tone. Also, as blood
flow increases back to the right heart of the person, vital organ
perfusion and function is enhanced. Another advantage is that heart
rate variability may also be increased and sympathetic tone may be
decreased. Such techniques may also be used to reduce the person's
anxiety level and to treat shock secondary to hypovolemia, sepsis
and heart failure. In some cases, the techniques may be used to
treat sleep disorders, such as sleep apnea, and to treat states of
hypo-perfusion, such as wound healing, stroke and diseases where
blood flow is compromised, including coronary artery disease. In
one particular treatment, the invention may be used to improve
blood flow to the muscles and brain, thereby reducing heart rate
and enhancing recovery from physical exertion. For example, as
intrathoracic pressures are reduced, more heart filling and
improved blood circulation results. The nervous system responds by
reducing the heart rate and overall the body recovers more quickly.
Such techniques may also be used before a person begins to
exercise.
[0007] The invention also includes a device for modulating a
person's autonomic function. The device comprises a housing having
an opening that is adapted to be interfaced with the person's
airway, and a valve system that is operable to regulate respiratory
gas flow through the housing and into the person's lungs due to
inhalation. The valve system is employed to assist in manipulating
intrathoracic pressures during inhalation to produce a vacuum
within the thorax to transiently decrease intrathoracic pressure
and thereby modulate the person's autonomic function. The valve
system may also be configured to permit respiratory gases to flow
to the person's lungs when the negative intrathoracic pressure
reaches a pressure in the range from about -2 cm H2O to about -30
cm H2O, and more preferably range from about -3 cm H2O to about -12
cm H2O in order to modulate the person's autonomic function.
[0008] In another embodiment, the invention provides a device for
decreasing intracranial or intraocular pressures. The device
comprises a housing having an inlet opening and an outlet opening
that is adapted to be interfaced with a person's airway. The device
further includes a valve system that is operable to regulate
respiratory gas flows through the housing and into the person's
lungs during spontaneous or artificial inspiration. The valve
system assists in lowering intrathoracic pressures during
inspiration to continuously or intermittently lower pressures in
the venous blood vessels that transport blood out of the head to
thereby reduce intracranial or intraocular pressures.
[0009] Such a device may also be used to facilitate movement of
cerebral spinal fluid. In so doing, intracranial pressures may be
further reduced. Such a device may therefore be used to treat those
suffering from head trauma associated with elevated intracranial
pressures as well as those suffering from heart conditions that
increase intracranial pressures.
[0010] In one aspect, the valve system is configured to open to
permit respiratory gasses to freely flow to the person's lungs when
the negative intrathoracic pressure reaches a pressure in the range
from about -2 cmH2O to about -20 cmH2O in order to reduce
intracranial or intraocular pressures. In this way, the negative
intrathoracic pressure is lowered until a threshold pressure is
reached, at which time the valve opens. The cycle may be repeated
continuously or periodically to repetitively lower intrathoracic
pressures.
[0011] The device may also include means for causing the person to
artificially inspire through the valve system. For example, the
device may utilize an electrode, an iron lung cuirass device, a
chest lifting device, a ventilator or the like.
[0012] In another embodiment, the device may comprise a means to
reduce intrathoracic pressure by applying a vacuum within the
airway. The vacuum may be adjusted in terms of frequency,
amplitude, and duration. This results in a decrease in intracranial
pressure in proportion to the degree of vacuum applied. Hence,
intracranial pressures may be reduced simply by manipulating airway
pressures to reduce intrathoracic pressures.
[0013] The device may further include a mechanism for varying the
level of impedance of the valve system. This may be used in
combination with at least one physiological sensor that is
configured to monitor at least one physiological parameter of the
person. In this way, the mechanism for varying the level of
impedance may be configured to receive signals from the sensor and
to vary the level of impedance of the valve system based on the
signals. Examples of sensors that may be used include those that
measure respiratory rate, intrathoracic pressure, intratracheal
pressure, blood pressure, heart rate, end tidal CO2, oxygen level,
intracranial perfusion, and intracranial pressure.
[0014] In one aspect, a coupling mechanism may be used to couple
the valve system to the person's airway. Examples of coupling
mechanisms include a mouthpiece, an endotracheal tube, and a face
mask.
[0015] A wide variety of valve systems may be used to repetitively
decrease the person's intrathoracic pressure. For example, valve
systems that may be used include those having spring-biased
devices, those having automated, electronic or mechanical systems
to occlude and open a valve lumen, duck bill valves, ball valves,
other pressure sensitive valve systems capable of opening a closing
when subjected to low pressure differentials triggered either by
spontaneous breathing and/or external systems to manipulate
intrathoracic pressures (such as ventilators, phrenic nerve
stimulators, iron lungs, and the like).
[0016] In another embodiment, the invention provides a method for
decreasing intracranial or intraocular pressures. According to the
method, a valve system is coupled to a person's airway and is
configured to at least periodically reduce or prevent respiratory
gases from flowing to the person's lungs. With the valve system
coupled to the airway, the person's negative intrathoracic pressure
is repetitively decreased to in turn repetitively lower pressures
in the venous blood vessels that transport blood out of the head.
In so doing, intracranial and intraocular pressures are reduced.
Such a method also facilitates movement of cerebral spinal fluid.
In so doing, intracranial pressures are further reduced. As such,
this method may also be used to treat a person suffering from head
trauma that is associated with elevated intracranial pressures as
well as those suffering from heart conditions that increase
intracranial pressures, such as atrial fibrillation and heart
failure.
[0017] The person's negative intrathoracic pressure may be
repetitively decreased as the person repeatedly inspires through
the valve system. This may be done by the person's own efforts
(referred to as spontaneous breathing), or by artificially causing
the person to repeatedly inspire through the valve system. For
example, the person may be caused to artificially inspire by
repeatedly stimulating the phrenic nerve, by manipulating the chest
with an iron lung cuirass device, by generating negative pressures
within the thorax using a ventilator, by applying a high frequency
ventilator that supplies oscillations at a rate of about 200 to
about 2000 per minute, or the like.
[0018] In another aspect, the level of impedance of the valve
system may be fixed or variable. If variable, at least one
physiological parameters of the person may be measured, and the
impedance level may be varied based on the measured parameters.
[0019] To couple the valve system to the airway, a variety of
techniques may be used, such as by using a mouthpiece, an
endotracheal tube, a face mask or the like. Further, the
respiratory gases may be prevented from entering the lungs through
the valve system until a negative intrathoracic pressure in the
range from about 0 cmH2O to about -25 cmH2O is achieved, at which
time the valve system permits respiratory gases to flow to the
lungs.
[0020] In another embodiment, the invention provides a method for
treating a person suffering from head trauma associated with
elevated intracranial pressures. According to the method, a
positive pressure breath is delivered to the person. Following the
positive pressure breath, respiratory gases are extracted from the
person's airway to create an intrathoracic vacuum. In turn, this
lowers pressures in the venous blood vessels that transport blood
out of the head to thereby reduce intracranial pressures. The steps
of delivering positive pressure breaths and extracting respiratory
gases are repeated to continue the treatment.
[0021] In one aspect, the delivery of the positive pressure breaths
and the extraction of gases are performed using a mechanical
ventilator. The respiratory gases may be extracted with a constant
extraction or a pulsed extraction.
[0022] In a further aspect, the breath may be delivered for a time
in the range for about 250 milliseconds to about 2 seconds. Also,
the breath may be delivered at a rate in the range from about 0.1
liters per second to about 5 liters per second. In another aspect,
the vacuum may be maintained at a pressure in the level from about
0 mmHg to about -50 mmHg. The vacuum may be maintained with a
negative flow or without any flow. The time that the positive
pressure breath is supplied relative to the time in which
respiratory gases are extracted may be in the range from about 0.5
to about 0.1.
[0023] A variety of equipment may be used to extract the
respiratory gases including mechanical ventilators, phrenic nerve
stimulators, ventilator bags, iron lung cuirass devices and the
like. In some cases, a threshold valve may also be coupled to the
person's airway. The threshold valve may be configured to open when
an adult's negative intrathoracic pressure exceeds about -5 cmH2O.
For pediatric cases, the valve may open when the pressure exceeds
about -2 cmH2O to about -5 cmH2O. In this way, when the person
inhales, the negative intrathoracic pressure may be lowered.
[0024] A variety of schemes may be used to deliver and extract
respiratory gases. For example, respiratory gases may be extracted
to achieve a pressure of about -5 mmHg to about -10 mmHg and then
kept generally constant until the next positive pressure breath. As
another example, the positive breath may be slowly delivered and
the intrathoracic pressure may be rapidly lowered to a pressure of
about -10 mmHg to about -20 mmHg and then gradually reduced towards
about 0 mmHg. As a further example, the intrathoracic pressure may
be slowly lowered to a pressure of about -20 mm Hg.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 is a flow chart illustrating one method for reducing
intracranial and intraocular pressures according to the
invention.
[0026] FIG. 2 is a perspective view of one embodiment of a facial
mask and a valve system that may be used to reduce intracranial and
intraocular pressures according to the invention.
[0027] FIG. 3 is a perspective view of the valve system of FIG.
2.
[0028] FIG. 4 is a cross sectional side view of the valve system of
FIG. 3.
[0029] FIG. 5 is an exploded view of the valve system of FIG.
3.
[0030] FIG. 6 is a schematic diagram of a system for reducing
intracranial and intraocular pressures according to the
invention.
[0031] FIG. 7 is a series of graphs illustrating the lowering of
intracranial pressures in an animal study.
[0032] FIG. 8 is a series of graphs illustrating the lowering of
intracranial pressures in another animal study.
[0033] FIG. 9A is a schematic diagram of a person's brain under
normal conditions.
[0034] FIG. 9B illustrates the brain of FIG. 9A after increased
swelling.
[0035] FIG. 10 shows three graphs illustrating the effect of
lowering intrathoracic pressure on intracranial pressure and right
atrial pressure.
[0036] FIG. 11 is a flow chart illustrating another method for
reducing intracranial and intraocular pressures according to the
invention.
[0037] FIGS. 12A-12C show three graphs illustrating patterns for
delivering a positive pressure breath and extracting respiratory
gases according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0038] In one aspect, the invention provides devices and techniques
for lowering intracranial and intraocular pressures. Such devices
and techniques may be particularly helpful with patients who have
suffered a traumatic brain injury. One way to lower such pressures
is by using a valve system that is coupled to a person's airway and
that is used to lower intrathoracic pressures. In so doing, the
valve systems may be used to accelerate the removal of venous blood
from the brain, thereby decreasing intracranial and intraocular
pressures. Other techniques may be used as well, such as by
creating a vacuum intermittently within the thorax. By reducing
intracranial pressures, movement of cerebral spinal fluid is also
enhanced. In so doing, intracranial pressures are further reduced
thereby providing further treatment for those suffering from head
trauma. In some cases, the valve systems may also be used to treat
the brain function in a person suffering from a heart condition
(atrial fibrillation, heart failure, cardiac tamponade, and the
like) that results in elevated intracranial pressures. Such heart
conditions may include, for example, atrial fibrillation or heart
failure. By reducing intracranial pressures, cerebral spinal fluid
movement and translocation is increased to help improve brain
function.
[0039] Intracranial pressures are regulated by the amount the
cerebral perfusion pressure, which is determined by the arterial
blood pressure to the head, the pressures within the skull, and the
pressures within the venous system that drains blood flow from the
brain. The devices and methods of the invention may be used to
enhance the egress of venous blood out of the brain, thereby
lowering intracranial pressures. To do so, the devices and methods
may be used to augment the intrathoracic vacuum effect each time a
patient inhales (or in the case of a non-breathing patient, each
time the pressure within the chest is manipulated to fall below
atmospheric pressure), thereby lowering the pressures in the thorax
and in the venous blood vessels that transport blood out of the
brain. The vacuum effect is transduced back into the brain, and as
a result, intracranial pressures are lowered with each inspiratory
effort. This in turn causes more venous blood to flow out of the
head than would otherwise be possible, resulting in lower
intracranial pressures and lower intraocular pressures.
[0040] Similar techniques may also be used to alter autonomic
nervous system function and result in at least a transient decrease
in heart rate and peripheral arterial resistance. For instance,
because of lowered intracranial pressures, an autonomic nervous
system-modulated decrease in sympathetic tone may result. This may
lead to a decrease in peripheral arterial resistance. Other results
that may be achieved using such techniques include an increased
heart rate variability and a reduction in the person's anxiety
level. Also, the techniques may be used to treat shock secondary to
hypovolemia, sepsis and heart failure. In some cases, the
techniques may be used to treat sleep disorders, such as sleep
apnea, and to treat states of hypo-perfusion, such as wound
healing, stroke and diseases where blood flow is compromised,
including coronary artery disease. In one particular treatment, the
invention may be used to improve blood flow to the muscles and
brain, thereby reducing heart rate and enhancing recovery from
physical exertion. The reduced intrathoracic pressures may result
in increased heart filling and circulation. As a result, the
nervous system may reduce heart rate, thereby allowing the body to
more quickly recover.
[0041] To prevent or impede respiratory gases from flowing to the
lungs, a variety of impeding or preventing mechanisms may be used,
including those described in U.S. Pat. Nos. 5,551,420; 5,692,498;
6,062,219; 5,730,122; 6,155,257; 6,234,916 and 6,224,562, and in
U.S. patent application Ser. No. 10/224,263, filed on Aug. 19, 2002
("Systems and Methods for Enhancing Blood Circulation", Attorney
Docket No. 16354-000115), 10/401,493, filed Mar. 28, 2003
("Diabetes Treatment Systems and Methods", Attorney Docket No.
16354-000116), 09/966,945, filed Sep. 28, 2001 and 09/967,029,
filed Sep. 28, 2001, the complete disclosures of which are herein
incorporated by reference. The valve systems may be configured to
completely prevent or provide resistance to the inflow of
respiratory gases into the patient while the patient inspires. For
valve systems that completely prevent the flow of respiratory
gases, such valves may be configured as pressure responsive valves
that open after a threshold negative intrathoracic pressure has
been reached.
[0042] For example, the resistance to the inflow of respiratory
gases may be set between about 0 cm H2O and about -25 cm H2O and
may be variable or fixed. More preferably, the valve system may be
configured to open when the negative intrathoracic pressure is in
the range from about -2 cmH2O to about -20 cmH2O. When attempting
to improve autonomic function, that valve may be set to open at
about -2 cm H2O to about -30 cm H2O, and more preferably range from
about -3 cm H2O to about -12 cm H2O.
[0043] Although not intended to be limiting, specific kinds of
impedance valves that may be used to reduce intracranial and
intraocular pressures include those having spring-biased devices,
automated/electronic and mechanical means to occlude and open a
valve lumen, duck bill valves, ball valves, and other pressure
sensitive valve systems capable of opening and closing when
subjected to low pressure differentials triggered either by
spontaneous breathing and/or external means to manipulate
intrathoracic pressure (such as ventilators, phrenic nerve
stimulators, an iron lung, and the like).
[0044] In the past, such threshold valve systems have been used to
increase the venous preload on the heart and to increase cardiac
output, stroke volume and blood pressure because of the augmented
effects of the intrathoracic vacuum on the subsequent cardiac
contraction. In contrast, the techniques of the invention function
by facilitating the removal of blood from the venous side of the
brain. Although there may be an increase in blood flow out of the
heart to the vital organs (including to the brain) when using such
valve systems, the effect of the valve systems on lowering of
intracranial pressures was quite unexpected because of the known
increase in blood flow to the brain. Remarkably, however, the
reduction of venous blood pressures from the brain remains
substantial when using the valve systems. Thus, despite the
increase in blood flow to the brain, the net effect of the valve
system is a decrease in intracranial pressures.
[0045] With the valve system coupled to the person's airway, the
negative intrathoracic pressure may be enhanced by inspiring
through the valve system. If the person is spontaneously breathing,
the person may simply breath through the valve system. If the
person is not breathing, artificial inspiration may be induced
using a variety of techniques, including electrical stimulation of
the diaphragm, a negative pressure ventilator such as a body
cuirass or iron lung, or a positive pressure ventilator capable of
also generating a vacuum between positive pressure ventilations. As
one example, at least some of the respiratory muscles, and
particularly the inspiratory muscles, may be stimulated to contract
in a repeating manner in order to cause the person to inspire
through the valve system, thereby increasing the magnitude and
prolonging the duration of negative intrathoracic pressure, i.e.,
respiratory muscle stimulation increases the duration and degree
that the intrathoracic pressure is below or negative with respect
to the pressure in the peripheral venous vasculature. Upon
contraction of the respiratory muscles, the patient will typically
"gasp". These techniques may be performed alone, or in combination
with a valve system.
[0046] Among the respiratory muscles that may be stimulated to
contract are the diaphragm, the chest wall muscles, including the
intercostal muscles and the abdominal muscles. Specific chest wall
muscles that may be stimulated to contract include those that
elevate the upper ribs, including the scaleni and
stemocleidomastoid muscles, those that act to fix the shoulder
girdle, including the trapezii, rhomboidei, and levatores angulorum
scapulorum muscles, and those that act to elevate the ribs,
including the serrati antici majores, and the pectorales majores
and minores as described generally in Leslie A. Geddes,
"Electroventilation--A Missed Opportunity?", Biomedical
Instrumentation & Technology, July/August 1998, pp. 401-414,
the complete disclosure of which is herein incorporated by
reference. Of the respiratory muscles, the two hemi diaphragms and
intercostal muscles appear to be the greatest contributors to
inspiration and expiration. The respiratory muscles may be
stimulated to contract in a variety of ways. For example, the
diaphragm may be stimulated to contract by supplying electrical
current or a magnetic field to various nerves or muscle bundles
which when stimulated cause the diaphragm to contract. Similar
techniques may be used to stimulate the chest wall muscles to
contract. A variety of pulse trains, pulse widths, pulse
frequencies and pulse waveforms may be used for stimulation.
Further, the electrode location and timing of pulse delivery may be
varied. In one particular aspect, an electrical current gradient or
a magnetic field is provided to directly or indirectly stimulate
the phrenic nerve.
[0047] To electrically stimulate the inspiratory motor nerves,
electrodes are preferably placed on the lateral surface of the neck
over the point where the phrenic nerve, on the chest surface just
lateral to the lower sternum to deliver current to the phrenic
nerves just as they enter the diaphragm, on the upper chest just
anterior to the axillae to stimulate the thoracic nerves, in the
oral pharyngeal region of the throat, or on the larynx itself.
However, it will be appreciated that other electrode sites may be
employed. For example, in one embodiment the respiratory muscles
are stimulated by a transcutaneous electrical impulse delivered
along the lower antero-lat margin of the rib cage. In one
embodiment, inspiration is induced by stimulating inspiratory
muscles using one or more electrodes attached to an endotracheal
tube or pharyngeal tube. To stimulate the diaphragm, the phrenic
nerve may be stimulated in the neck region near C3-C7, such as
between C3, C4 or C5, or where the phrenic nerves enter the
diaphragm. Alternative techniques for stimulating diaphragmatic
contraction include magnetic field stimulation of the diaphragm or
the phrenic nerve. Magnetic field stimulation may also be employed
to stimulate the chest wall muscles. Electrical field stimulation
of the diaphragm or the chest wall muscles may be accomplished by
placing one or more electrodes on the skin, preferably in the
vicinity of the neck or the lower rib cage (although other
locations may be employed) and then providing an electrical voltage
gradient between electrodes that induces transcutaneous current
flow to stimulate the respiratory muscles to contract. Still
further, subcutaneous electrodes may also be used to stimulate
respiratory muscle contraction. Other techniques are described in
U.S. Pat. No. 6,463,327, the complete disclosure of which is herein
incorporated by reference.
[0048] The valve systems may have a fixed actuating pressure or may
be variable so that once a desired negative intrathoracic pressure
is reached, the resistance to flow may be lessened. Further, the
valves of the invention may be configured to be variable, either
manually or automatically. The extent to which the resistance to
flow is varied may be based on physiological parameters measured by
one or more sensors that are associated with the person being
treated. As such, the resistance to flow may be varied so that the
person's physiological parameters are brought within an acceptable
range. If an automated system is used, such sensors may be coupled
to a controller which is employed to control one or more mechanisms
that vary the resistance or actuating pressure of the inflow valve
as generally described in the references that have been
incorporated by reference.
[0049] Hence, the valve systems of the invention may also
incorporate or be associated with sensors that are used to detect
changes in intrathoracic pressures or other physiological
parameters. In one aspect, the sensors may be configured to
wirelessly transmit their measured signals to a remote receiver
that is in communication with a controller. In turn the controller
may use the measured signals to vary operation of the valve systems
described or incorporated by reference herein. For example, sensors
may be used to sense blood pressure, pressures within the heart,
intrathoracic pressures, positive end expiratory pressure,
respiratory rate, intracranial pressures, intraocular pressures,
respiratory flow, oxygen delivery, temperature, blood pH, end tidal
CO2, tissue CO2, blood oxygen, cardiac output or the like. Signals
from these sensors may be wirelessly transmitted to a receiver.
This information may then be used by a controller to control the
actuating pressure or the resistance of an inflow valve as
described in the references incorporated herein by reference.
[0050] The techniques for reducing intracranial pressures may be
used in a variety of settings. For example, the techniques may be
used in person's who are spontaneously breathing, those who are not
breathing but whose hearts are beating, and those in cardiac
arrest. In the latter case, the techniques may use some means to
create a vacuum intermittently within the thorax during the
performance of CPR. This could be by using a valve system or some
other type of pressure manipulation system. Further, such systems
may be used in other settings as well, including when the person is
breathing.
[0051] FIG. 1 is flow diagram illustrating one method for reducing
intracranial or intraocular pressures, as well as for modulating
autonomic function. As shown in step 10, the process proceeds by
coupling a valve system to the person's airway. Any kind of
coupling mechanism may be used, such as by a mouthpiece, an
endotracheal tube, a face mask, or the like. Further, any of the
valve systems described or incorporated herein by reference may be
used. In step 20, the person's negative intrathoracic pressure is
repetitively decreased (either artificially or by spontaneous
breathing). Examples of techniques to artificially reduce the
negative intrathoracic pressure include use of an iron lung cuirass
device, a ventilator that is capable of generating negative
pressures, a ventilator that is capable of providing high frequency
oscillations at a rate of about 200 to about 2000 per minute, a
phrenic nerve stimulator, or the like. As the person's negative
intrathoracic pressure is repeatedly decreased while the valve
system is coupled to the airway, the pressures in the venous
vessels that transport blood out of the head are also lowered. In
so doing, intracranial and intraocular pressures are reduced. This
in turn may produce an autonomic nervous system-modulated decrease
in sympathetic tone and a decrease in peripheral arterial
resistance.
[0052] As shown in step 30, various physiological parameters of the
person may optionally be measured. Examples of such parameters
include respiratory rate, intrathoracic pressure, intertracheal
pressure, intracranial pressure, intracranial blood flow,
intraocular pressure, blood pressure, heart rate, end tidal
CO.sub.2, oxygen saturation, and the like. Further, as shown in
step 40, the valve system's actuating threshold level may
optionally be varied based on the measured physiological
parameters. This may be done to maximize the amount of blood drawn
out of the brain or simply to monitor the patient's condition to
insure that the patient remains stable.
[0053] FIG. 2 illustrates one embodiment of a facial mask 100 to
which is coupled a valve system 200. Mask 100 is configured to be
secured to a patient's face so as to cover the mouth and nose. Mask
100 and valve system 200 are examples of one type of equipment that
may be used to lower intrathoracic pressures and thereby lower
intracranial and intraocular pressures. However, it will be
appreciated that other valve systems and other coupling
arrangements may be used including, for example, those previously
referenced. As such the invention is not intended to be limited to
the specific valve system and mask described below.
[0054] Referring also to FIGS. 3-5, valve system 200 will be
described in greater detail. Valve system 200 includes a valve
housing 202 with a socket 204 into which a ball 206 of a
ventilation tube 208 is received. In this way, ventilation tube 208
may rotate about a horizontal axis and pivot relative to a vertical
axis. A respiratory source, such as a ventilation bag, may be
coupled to tube 208 to assist in ventilation. Disposed in
ventilation tube 208 is a filter 210 that is spaced above a duck
bill valve 212. A diaphragm holder 214 that holds a diaphragm 216
is held within housing 202. Valve system 200 further includes a
patient port 218 that is held in place by a second housing 220.
Housing 220 conveniently includes tabs 222 to facilitate coupling
of valve system 200 with facial mask 100. Also held within housing
220 is a check valve 224 that comprises a spring 224a, a ring
member 224b, and an o-ring 224c. Spring 224a biases ring member
224b against patient port 218. Patient port 218 includes bypass
openings 226 that are covered by o-ring 224c of check valve 224
until the pressure in patient port 218 reaches a threshold negative
pressure to cause spring 224a to compress.
[0055] When the patient is actively ventilated, respiratory gases
are forced through ventilation tube 208. The gases flow through
filter 210, through duck bill valve 212, and forces up diaphragm
214 to permit the gases to exit through port 218. Hence, at any
time the patient may be ventilated simply by forcing the
respiratory gases through tube 208.
[0056] During the exhalation phase of a breathing cycle, expired
gases flow through port 218 and lift up diaphragm 214. The gases
then flow through a passage 227 in ventilation tube 208 where they
exit the system through openings 229 (see FIG. 3).
[0057] During the inhalation phase of a breathing cycle, valve
system 200 prevents respiratory gases from flowing into the lungs
until a threshold negative intrathoracic pressure level is
exceeded. When this pressure level is exceeded, check valve 224 is
pulled downward as springs 224a are compressed to permit
respiratory gases to flow through openings 226 and to the patient's
lungs by initially passing through tube 208 and duck bill valve
212. Valve 224 may be set to open when the negative intrathoracic
pressure is in the range from about 0 cm H2O to about -25 cm H2O,
and more preferably from about -2 cm H2O to about -20 cm H2O when
lowering intracranial pressures. To modulate autonomic function,
the cracking pressure may be in the range from about -2 cm H2O to
about -30 cm H2O, and more preferably range from about -3 cm H2O to
about -12 cm H2O for flow rates of about 30 to about 50 liters per
minute. Hence, the magnitude and duration of negative intrathoracic
pressure may be enhanced during patient inhalation by use of valve
system 200. Once the intrathoracic pressure falls below the
threshold, recoil spring 224a again close check valve 224. In this
way, pressure within the venous blood vessels that transport blood
out of the brain are also lowered. In so doing, more blood is drawn
out of the brain to reduce intracranial and intraocular pressures.
As a result, sympathetic tone may be decrease resulting in a
decrease in peripheral arterial resistance.
[0058] Any of the valve systems described herein may be
incorporated into a treatment system 300 as illustrated in FIG. 6.
System 300 may conveniently include facial mask 100 and valve
system 200, although any of the valve systems or interfacing
mechanisms described herein or the like may be used. Valve system
200 may conveniently be coupled to a controller 310. In turn,
controller 310 may be used to control the impedance level of valve
system 200 in a manner similar to any of the embodiments described
or incorporated herein. The level of impedance may be varied based
on measurements of physiological parameters, or using a programmed
schedule of changes. System 300 may include a wide variety of
sensors and/or measuring devices to measure any of the
physiological parameters described herein. These sensors or
measuring devices may be integrated within or coupled to valve
system 200 or facial mask, or may be separate.
[0059] For example, valve system 200 may include a pressure
transducer for taking pressure measurements (such as intrathoracic
pressures, intracranial pressures, intraocular pressures), a flow
rate measuring device for measuring the flow rate of air into or
out of the lungs, or a CO2 sensor for measuring expired CO2.
[0060] Examples of other sensors or measuring devices include a
heart rate sensor 330, a blood pressure sensor 340, and a
temperature sensor 350. These sensors may also be coupled to
controller 310 so that measurements may be recorded. Further, it
will be appreciated that other types of measuring devices may be
used to measure various physiological parameters, such as oxygen
saturation and/or blood levels of O2, blood lactate, blood pH,
tissue lactate, tissue pH, blood pressure, pressures within the
heart, intrathoracic pressures, positive end expiratory pressure,
respiratory rate, intracranial pressures, intraocular pressures,
respiratory flow, oxygen delivery, temperature, end tidal CO2,
tissue CO2, cardiac output or the like.
[0061] In some cases, controller 310 may be used to control valve
system 200, to control any sensors or measuring devices, to record
measurements, and to perform any comparisons. Alternatively, a set
of computers and/or controllers may be used in combination to
perform such tasks. This equipment may have appropriate processors,
display screens, input and output devices, entry devices, memory or
databases, software, and the like needed to operate system 300.
[0062] A variety of devices may also be coupled to controller 310
to cause the person to artificially inspire. For example, such
devices may comprise a ventilator 360, an iron lung cuirass device
370 or a phrenic nerve stimulator 380. Ventilator 360 may be
configured to create a negative intrathoracic pressure within the
person, or may be a high frequency ventilator capable of generating
oscillations at about 200 to about 2000 per minute.
EXAMPLE 1
[0063] The following is a non-limiting example illustrating how
intracranial pressures may be lowered according to the invention.
In this example, 30 kg pigs were anesthetized with propofol. Using
a micromannometer-tipped electronic Millar catheter inserted below
the dura, intracranial pressures were measured continuously in the
spontaneously breathing pigs. Intrathoracic pressures (ITP) were
recorded using a Millar catheter placed in the trachea at the level
of the carina. After stabilizing the pigs blood pressure, heart
rate, and ventilation rate, intracranial pressures (ICP) and
intrathoracic pressures were recorded, with 0 cmH2O inspiratory
impedance and then with inspiratory impedances of 5, 10, 15, and 20
cm H2O. Inspiratory impedance was achieved using an impedance
threshold valve (ITV) as described in FIGS. 2-5.
[0064] At base, the intracranial pressure was approximately 8/4
mmHg. With increasing amounts of inspiratory impedance, the
intracranial pressure was lowered proportionally as shown in FIG.
7. The intracranial pressure was 6/-2 mmHg when the pig breathed
through an impedance of 20 cm H2O. These findings were observed in
multiple pig studies and were reproducible. Next, the Millar
catheter was inserted 3 cm into the pig's brain. The intracranial
pressure increased secondary to the trauma associated with the
insertion of the probe. The intracranial pressure increased to
25/22 mmHg at the new baseline. Next, the impedance threshold valve
was evaluated at different levels of resistance (FIG. 8). Again,
there was a decrease in intracranial pressure proportional to the
degree of inspiratory impedance.
EXAMPLE 2
[0065] In this example, intracranial pressures were increased in
the setting of recovery from cardiac arrest. The example used a pig
model with ventricular fibrillation for 6 minutes followed by
cardiopulmonary resuscitation for 6 minutes, followed by
defibrillation. Spontaneous breathing resulted in an up to 50%
decrease in intracranial pressures when the animals breathed
through an inspiratory impedance of 10 cm H2O using a valve system
similar to Example 1.
[0066] In all examples above, the intrathoracic pressure decreased
relative to the rest of the body, creating a suction effect that
reduced the pressure in the venous blood vessels draining the
brain, thereby reducing intracranial pressures.
[0067] The invention further provides techniques and devices for
reducing intracranial pressure (ICP) by facilitating movement of
cerebral spinal fluid (CFS). There are a number of causes of
increased ICP including: head injury, ischemia, osmolar imbalance,
cerebral edema, tumors, complications of dialysis, infections,
stroke, hypertensive crises. Each can result in a slow, and in some
cases, an acute rise in the ICP. The solid matter of the brain
contents makes up about 80-85% of the material enclosed by the
skull. Cerebral blood volume accounts for 3-6% and CSF for 5-15%.
See, Anesthesia, Third Edition Editor, Ron Miller. Chapter authors:
Shapiro and Drummond. Chapter 54 (1990), the complete disclosure of
which is herein incorporated by reference. CSF moves within the
brain from its site of production to its site of reabsorption in
the brain in an unimpeded manner under normal physiological states.
Since the contents in the brain are practically incompressible, a
change in volume of any one of the three major components (brain
matter, blood volume, CSF volume) results in a reciprocal change in
one or both of the other brain components. When the volume of the
brain expands, secondary to an increase in the non-CSF
component(s), some of the CSF is forced to other locations,
including through the foramen magnum (hole in skull connecting
skull to space where the spinal cord is located) and into the CSF
fluid space surrounding the spinal cord. When the non-CSF
components expand in volume or size, the intracranial pressure
rises. Normal ICP levels are 10-15 mmHg when supine. At levels
greater than 15-20 mmHg, damage to the brain can occur secondary to
compression and resultant tissue ischemia (lack of adequate blood
flow). A reduction in ICP levels can be achieved by a number of
clinical interventions including water restriction, diuretics,
steroids, hyperventilation, a reduction of cerebral venous
pressure, hypothermia, CSF drainage, and surgical
decompression.
[0068] Increased ICP results in reduced CSF fluid movement and
translocation. CSF fluid production generally remains constant
(about 150 ml/day) despite elevated ICP. CSF fluid reabsorption is
can be slowed by elevated ICP. By using the valve systems described
herein, central venous pressures may be reduced. In turn, this
results in a decrease in ICP and results in an increase in CSF
fluid movement or translocation and reabsorption. This results in a
further reduction in ICP.
[0069] The valve systems of the invention may be used in
spontaneously breathing individuals, in patients ventilated with
negative pressure ventilation or in patients ventilated with a
ventilator that causes a decrease in central venous pressures for
at least a portion of the respiratory cycle. Each time the
intrathoracic pressure is reduced with the valve systems of the
invention, there is a concomitant reduction in ICP and an increase
in the movement of CSF. In other words, there is an increase in the
difference between the peak and trough of the ICP wave form when
using the valve systems. The sinusoidal movement occurs in
spontaneously breathing people because of the change in pressure in
the thorax that is transmitted to the brain via the venous blood
vessels. The normally fluctuating CSF pressures (the pressure
increases and decreases with each inspiration) are altered by the
valve systems. More specifically, the valve systems create a lower
trough value thereby creating an overall created change in the ICP
with each inspiration. In the non-breathing patient, a similar
effect can be produced with the valve systems when used with a
variety of ventilator devices, including an iron lung, a phrenic
nerve stimulator (such as those described in U.S. Pat. Nos.
6,234,985; 6,224,562; and 6312399, incorporated herein by
reference), a suction cup on the chest that is used to periodically
expand the chest and the like.
[0070] Increased CSF fluid movement results in an overall improved
metabolic state for the brain. This is shown schematically in FIGS.
9A and 9B. In FIG. 9A, the brain 400 is shown under normal
conditions. The brain 400 is surrounded by CSF 402 which is
produced at a site 404. The CFS in turn is surrounded by the skull
406. Blood enters brain 400 through an artery 408 and exits through
a vein 410. Vein 410 also includes a site 412 of CFS drainage.
Shown in FIG. 9A is an arrow showing the direction of CFS flow when
draining. Extending from brain 400 is the spinal cord 414 that is
surrounded by the foramen magnum 416.
[0071] In FIG. 9B, the brain 400 is significantly swollen which
reduces the space 402 where the CFS is located. The swelling of the
brain 400 can cause blockage of CSF to the spinal cord 414 as shown
by arrow 418. Also, movement of CSF to site 412 is reduced to
hinder movement of CSF out of the skull 406.
[0072] By treating the elevated ICP associated with all of the
conditions noted above using the valve systems described herein,
brain swelling can be reduced. In so doing, CFS movement and fluid
translocation is increased under those same conditions. This
results in a further decrease in intracranial pressure as the CSF
is able to relocate.
[0073] Referring now to FIG. 10, the effects of contracting the
atria of the heart on ICP will be described. As shown, contraction
of the atria results in a phasic movement in ICP. This can be most
clearly demonstrated during cardiac ventricular fibrillation. In
that setting, the atria often beat spontaneously and the pressure
of each contraction and relaxation waveform is transmitted
immediately to the brain and is reflected in nearly identical
fluctuations in ICP. The inventor has discovered that the fluid
systems (venous blood vessels and CSF) are so closely linked, that
subtle changes in the heart rhythm result in immediate changes in
CSF pressure. Thus, in some patients with significant heart
rhythms, or significant heart failure, the rise in right heart
pressures as a result of these conditions results in an increase in
ICP. Such rises in ICP can lead to a decrease in cerebral
perfusion, since cerebral perfusion is determined by the pressure
of the blood entering the brain (mean arterial pressure) minus the
pressure of the blood leaving the brain (ICP and central venous
pressure). Use of the valve and intrathoracic vacuum systems
described herein will result in a decrease in intrathoracic
pressure. As shown in FIG. 10, the downwardly pointing arrows
represent the timing of each inhalation through the valve system.
In the baseline state, before the onset of atrial fibrillation,
each inspiration (small arrows) results in a reduction in ITP, a
reduction of right atria pressure, a reduction in central venous
pressures, and then an immediate reduction in ICP. With the onset
of atrial fibrillation, the intracranial pressure rises and the
sinusoidal pattern of ICP amplitude changes becomes dampened. As
soon as the animal begins to inspire through an inspiration
impedance of -10 cm H20 there is an immediate decrease in
intrathoracic pressure (ITP), an immediate decrease in right atrial
(RA) pressures, and an immediate decrease in intracranial pressure
(ICP) along with the restoration of a sinusoidal fluctuation in ICP
with each inspiration. With elevated ICP, inspiration through the
impeding means results in a decrease in ICP, increased cerebral
spinal fluid flow, and a decrease in cerebral ischemia secondary to
increased cerebral perfusion. As such, the valve systems can used
in patients with heart rhythms, such as atrial fibrillation, or
patients with heart failure who have increased ICP in order to
reduce their ICP, increase CSF fluid movement and translocation,
and ultimately help them to improve their brain function.
[0074] Hence, the amount of inspiratory resistance, or the amount
of negative intrathoracic pressure generation (which may be
generated using a variety of techniques) can be controlled or
regulated by feedback from measurement of ICP, blood pressure,
respiratory rate, or other physiological parameters. Such a system
could include a closed loop feedback system.
[0075] FIG. 11 is a flow chart illustrating another method for
treating a person suffering from head trauma associated with
elevated intracranial pressures. In so doing, it will be
appreciated that such techniques may also be used to treat those
suffering from low blood pressure or those in cardiac arrest, among
others. The techniques are particularly useful in cases where the
person is not breathing, although in some cases they could be used
for breathing patients as well.
[0076] In a broad sense, when treating a person suffering from head
trauma, a person's intrathoracic pressure is lowered to decrease
intracranial pressures. In turn, this assists in reducing secondary
brain injury. As shown in step 500, equipment may be coupled to the
person to assist in lowering the person's intrathoracic pressure. A
wide variety of equipment and techniques may be used to decrease
the intrathoracic pressure, including using a mechanical ventilator
capable of extracting respiratory gases, such as the one described
in U.S. Pat. No. 6,584,973, a phrenic nerve or other muscle
stimulator (with or without the use of an impedance mechanism, such
as those described in U.S. Pat. Nos. 5,551,420; 5,692,498;
6,062,219; 5,730,122; 6,155,257; 6,234,916 and 6,224,562) such as
those described in U.S. Pat. Nos. 6,234,985; 6,224,562; 6,312,399;
and 6,463,327, an iron lung device, a thoracic vest capable of
pulling outward on the chest wall to create an intrathoracic vacuum
similar to the effect of an iron lung, a ventilatory bag, such as
the one described in copending U.S. application Ser. No.
10/660,366, filed Sep. 11, 2003 (attorney docket no. 16354-005400),
filed on the same date as the present application, and the like.
The complete disclosures of all these references are herein
incorporated by reference. For breathing patients, a threshold
valve as described above and that is set to open when about 5 cmH20
is generated during an inhalation may be used to enhance the
person's negative intrathoracic pressure.
[0077] When the person is not breathing, a positive pressure breath
is delivered to the person as illustrated in step 502. This may be
done with a mechanical ventilator, a ventilatory bag, mouth to
mouth, and the like. This is followed by an immediate decrease in
intrathoracic pressure. This may be done by extracting or expelling
respiratory gases from the patient's lungs as shown in step 504.
Any of the techniques described above may be used to lower the
intrathoracic pressure. Such a reduction in intrathoracic pressure
also lowers central venous pressure and intracranial pressure.
[0078] The vacuum effect during the expiratory phase may be
constant, varied over time or pulsed. Examples of different ways to
apply the vacuum are described later with respect to FIGS. 12A-12C.
The initial positive pressure breath may be supplied for a time of
about 250 milliseconds to about 2 seconds, and more preferably from
about 0.75 seconds to about 1.5 seconds. The respiratory gases may
be extracted for a time that is about 0.5 to about 0.1 to that of
the positive pressure breath. The positive pressure breath may be
delivered at a flow rate in the range from about 0.1 liters per
second to about 5 liters per second, and more preferably from about
0.2 liters per second to about 2 liters per second. The expiratory
flow (such as when using a mechanical ventilator) may be in the
range from about 0.1 liters per second to about 5 liters per
second, and more preferably from about 0.2 liters per second to
about 2 liters per second. The vacuum may be maintained with a
negative flow or without any flow. The vacuum may be in the range
from about 0 mmHg to about -50 mmHg, and more preferably from about
0 mmHg to about -20 mmHg.
[0079] As shown in step 506, the process of delivering a positive
pressure breath and then immediately lowering intrathoracic
pressures may be repeated as long as necessary to control
intracranial pressures. Once finished, the process ends at step
508.
[0080] The manner in which positive pressure breaths and the vacuum
are created may vary depending upon a particular application. These
may be applied in a variety of waveforms having different durations
and slopes. Examples include using a square wave, biphasic (where a
vacuum is created followed by positive pressure, decay (where a
vacuum is created and then permitted to decay), and the like. Three
specific examples of how this may occur are illustrated in FIGS.
12A-12C, although others are possible. For convenience of
discussion, the time during which the positive pressure breath
occurs may be defined in terms of the inspiratory phase, and the
time during which the intrathoracic pressure is lowered may be
defined in terms of the expiratory phase. The positive pressure
breaths may occur at about 10 to about 16 breaths per minute, with
the inspiratory phase lasing about 1.0 to about 1.5 seconds, and
the expiration phase lasing about 3 to about 5 seconds. As shown in
FIG. 12A, respiratory gases are quickly supplied up to a pressure
of about 22 mmHg. This is immediately reversed to a negative
pressure of about -10 mmHg. This pressure is kept relatively
constant until the end of the expiratory phase where the cycle is
repeated.
[0081] In FIG. 12B, the positive pressure is more slowly applied.
When reaching a pressure of about 10 to about 15 mmHg, the pressure
is rapidly reversed to a negative pressure of about -20 mmHg. The
negative pressure gradually declines to about 0 mmHg at the end of
the expiratory phase. The cycle is then repeated. Hence, in the
cycle of FIG. 12B, the positive pressure is reduced compared to the
cycle in FIG. 12A, and the negative pressure is initially lower,
but allowed to gradually increase. The technique is designed to
help reduce a possible airway collapse.
[0082] In FIG. 12C, the positive pressure is brought up to about 20
mmHg and then immediately brought down to about 0 mmHg. The
negative pressure is then gradually increased to about -20 mmHg
toward the end of the expiratory phase. This cycle is designed to
help reduce a possible airway collapse.
[0083] The following examples illustrate the effectiveness of a
threshold valve system to modulate autonomic function. In Examples
3-5, a threshold valve system (also referred to as an inspiratory
impedance threshold device) similar to the ones described herein
(see FIGS. 2-5) is interfaced to an airway.
EXAMPLE 3
[0084] In this example, blood pressure changes and survival rate
are evaluated in severe hemorrhagic shock treated with an
inspiratory impedance threshold device (ITD) set to prevent
inspiratory airflow until the intratracheal pressure falls below
-10 cm H2O without affecting expiration.
[0085] Design: Randomized.
[0086] Setting: University animal laboratory.
[0087] Subjects: Yorkshire-cross pigs (22-31 kg).
[0088] Intervention: Controlled bleeding of 50% of calculated blood
volume followed by treatment with an ITD or observation for 90
minutes. Prior to bleeding, all the animals were intubated and
anesthetized but allowed to spontaneously breathe. After 90 minutes
of treatment, saline was administered and the animals were allowed
to recover.
[0089] Measurements and main results: Systolic blood pressure after
ten minutes of treatment with the ITD was higher in the treatment
group than in the control group (70.3.+-.5.8 vs. 50.1.+-.3.1 mmHg
respectively, P<0.01). All of the pigs in the control group died
within 65 min whereas 7/8 (87%) treated with an ITD survived for 90
minutes (P<0.001). During the recovery phase, one animal in the
treatment group never woke up from anesthesia and 6/8 (75%)
survived past 3 hours. No focal neurological defects were found
after recovery. Treatment with the ITD was not associated with
hypoxia.
[0090] Conclusion: ITD treatment during hemorrhagic shock improved
blood pressure and increased survival rates in spontaneously
breathing pigs.
EXAMPLE 4
[0091] Objective: An inspiratory impedance threshold device (ITD)
was evaluated in spontaneously breathing animals with hypotension
to determine if it could help improve systemic arterial pressures
when fluid replacement was not immediately available.
[0092] Design: Prospective, randomized
[0093] Setting: Animal laboratory
[0094] Subjects: Female farm pigs (wt 28-33 kg)
[0095] Interventions: Anesthetized spontaneously breathing pigs
were treated with an ITD, with cracking pressures from 0 to -20
cmH2O. Four separate experiments were performed:
[0096] A. Initial studies in normotensive and hypovolemic
hypotensive pigs (n=7) focused on the effects of 4 different ITD
cracking pressures (-5, -10, -15, -20 cm H.sub.2O) on hemodynamic
variables;
[0097] B. Pigs were hemorrhaged to a systolic blood pressure (SBP)
of 50-55 mmHg, and then treated with a sham (n=9) or active ITD
(-12 cmH.sub.2O) (n=9);
[0098] C. The effect of the ITD (-12 cmH.sub.2O) on arterial and
mixed venous gases was evaluated in hypotensive hypovolemic pigs
(n=7);
[0099] D. Cardiac output was measured in hypotensive hypovolemic
pigs (n=7) by thermodilution before and after treatment with the
ITD (-12 cmH.sub.2O) (n=9).
[0100] Methods and Main Results: During initial studies with both
normovolemic and hypovolemic pigs, sequential increases in
inspiratory impedance resulted in a significant increase in SBP;
whereas diastolic left ventricular (dLV) and right atrial (dRA)
pressures decreased significantly and proportionally to the level
of impedance. When comparing the sham versus active ITD (-12 cmH2O)
in hypotensive pigs, SBP (mean .+-.SEM) with active ITD treatment
rose from 70.+-.2 mmHg to 105.+-.4 mmHg (p<0.01). Pressures in
the control group remained at 70.+-.4 mmHg (p<0.01). Heart rates
in the animals treated with the active ITD (160.+-.2 bpm) were
significantly lower than in the controls (169.+-.-3
bpm)(p<0.02). Cardiac output increased by nearly 25% (p<0.01)
with the active ITD when calculated using the mixed gas equation
and when determined by thermodilution.
[0101] Conclusions: These studies demonstrate that it is feasible
to use a device that creates inspiratory impedance in spontaneously
breathing normotensive and hypotensive pigs to increase blood
pressure and enhance cardiopulmonary circulation in the absence of
immediate fluid resuscitation.
EXAMPLE 5
[0102] Increased negative intrathoracic pressure during spontaneous
inspiration through an impedance threshold device (ITD) causes an
elevation in systemic arterial blood pressure in humans. The
hypothesis was that the acute increase in blood pressure induced by
breathing through an ITD would be associated with increased stroke
volume (SV) and cardiac output (CO). This hypothesis was tested by
measuring hemodynamic and respiratory responses in 10 female and 10
male subjects during two separate ITD conditions: (a) breathing
through a face mask with an ITD set at approximately 6 cm H.sub.2O;
and, (b) breathing through the same face mask with a sham ITD
(control). The duration of ITD breathing was 14 min. The order of
the two experimental conditions was counterbalanced, and each
experiment was performed on a separate day. SV was measured by
thoracic bioimpedance. All hemodynamic measurements were repeated 5
min after cessation of ITD breathing. Compared with the control
(sham) condition, ITD produced higher SV (124.+-.3 vs 137.+-.3 ml,
P=0.013), HR (63.+-.3 vs 68.+-.3 ml, P=0.049), CO (7.69 vs 9.34
liters/min, P=0.001), and SBP (115.+-.2 to 122.+-.2 mmHg, P=0.005)
without affecting expired minute ventilation volume (6.2.+-.0.4 to
6.5.+-.0.4 liters/min, P=0.609). There were no gender effects and
all hemodynamic responses returned to control (sham) levels by 5
min after cessation of ITD breathing.
[0103] Conclusions: ITD breathing at relatively low impedance can
increase arterial blood pressure in otherwise healthy subjects by
increasing SV and CO. The ITD may therefore provide short-term
protection against cardiovascular collapse induced by orthostatic
stress or hemorrhage.
[0104] The invention has now been described in detail for purposes
of clarity and understanding. However, it will be appreciated that
certain changes and modifications may be practiced within the scope
of the appended claims.
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