U.S. patent application number 15/652376 was filed with the patent office on 2018-06-07 for method and device for non-invasive anatomical and systemic cooling and neuroprotection.
The applicant listed for this patent is THE JOHNS HOPKINS UNIVERSITY. Invention is credited to Tandri Harikrishna, Menekhem Muz Zviman.
Application Number | 20180153737 15/652376 |
Document ID | / |
Family ID | 48903572 |
Filed Date | 2018-06-07 |
United States Patent
Application |
20180153737 |
Kind Code |
A1 |
Harikrishna; Tandri ; et
al. |
June 7, 2018 |
METHOD AND DEVICE FOR NON-INVASIVE ANATOMICAL AND SYSTEMIC COOLING
AND NEUROPROTECTION
Abstract
The present invention provides a method and device for
non-invasive anatomical and systemic cooling, fluid removal and/or
energy removal. The method and device provide for removal of fluid
and cooling of various bodily fluid-containing spaces or surfaces,
such as mucus-containing spaces or surfaces via delivery of a dry
fluid not including a coolant into or upon the mucus-containing
space or surface. Exposure of such mucus to the dry fluid results
in evaporation of body fluid, removal of energy, cooling of the
anatomical feature, and systemic cooling. In this fashion,
therapeutic hypothermia may be achieved to provide for
neuroprotection of various organs after ischemic insult, such the
brain after cardiac arrest. Similarly, excess fluid removal may be
achieved for treatment of cardiogenic shock or other conditions
that cause significant fluid build-up, especially in cases of
compromised renal function. Additionally, the invention may be used
to reduce fever, and other conditions where removal of heat, energy
and/or water are beneficial.
Inventors: |
Harikrishna; Tandri;
(Ellicott City, MD) ; Zviman; Menekhem Muz;
(Belcamp, MD) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
THE JOHNS HOPKINS UNIVERSITY |
Baltimore |
MD |
US |
|
|
Family ID: |
48903572 |
Appl. No.: |
15/652376 |
Filed: |
July 18, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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13751617 |
Jan 28, 2013 |
9744071 |
|
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15652376 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 7/0085 20130101;
A61F 2007/126 20130101; A61F 2007/0065 20130101; A61F 2007/0069
20130101 |
International
Class: |
A61F 7/00 20060101
A61F007/00 |
Claims
1.-22. (canceled)
22. A device for inducing evaporation of a fluid from a bodily
fluid-containing space in a mammal, the device comprising: a
housing defining an airflow path therein; said housing containing a
fan configured to draw ambient air into the airflow path of said
housing and a dehumidifier to dehumidify said ambient air drawn
into said housing; said housing also containing an airflow delivery
port in communication with an external surface of said housing at
an air outlet side of said airflow path; said device further
comprising a conduit comprising: a proximal end, a distal end, a
first lumen extending between the proximal and distal ends, and one
or more dehumidified air delivery ports at the distal end in fluid
communication with the first lumen, said proximal end of said
conduit configured to connect to said airflow delivery port of said
housing; and wherein the device is configured such that ambient air
is drawn into the housing of the device by said fan, said ambient
air is dehumidified by said dehumidifier, and dehumidified air is
forced by said fan out of said housing via said airflow delivery
port and into said conduit to flow distally along the first lumen
through the dehumidified gas delivery ports to contact the bodily
fluid-containing space.
23. The device of claim 22, further comprising: c) a second lumen
extending toward the distal end of the conduit; d) one or more
return ports at the distal end in fluid communication with the
second lumen; and e) an exhaust port in fluid communication with
the proximal end of the second lumen; wherein the device is
configured such that dehumidified air flows distally along the
first lumen through the fluid delivery ports and air that has
contacted said bodily fluid containing space reenters the second
lumen through the return ports.
24. (canceled)
25. The device of claim 22, further comprising a temperature
sensor.
26. The device of claim 25, wherein the temperature sensor is
disposed at the distal tip of the conduit.
27. The device of claim 26, wherein the temperature sensor
comprises means to adjust fluid flow through the conduit.
28. The device of claim 24, further comprising a pressure
sensor.
29. The device of claim 28, wherein the pressure sensor is disposed
at the distal tip of the conduit.
30. The device of claim 28, wherein the pressure sensor comprises
means to adjust flow of air through the conduit.
31. The device of claim 22, wherein the device is configured to
deliver the dehumidified air to the lungs, trachea, oral cavity,
nasopharynx, nostrils, gastro-intestinal system, stomach,
peritoneal, or urinary bladder.
32. The device of claim 22, wherein the dehumidified air delivery
ports are disposed proximal to the return ports.
33. The device of claim 22, further comprising a fluid flow
regulator.
34. The device of claim 23, wherein the exhaust comprises means for
generating suction to facilitate flow of the air through the return
ports into the second lumen.
35. The device of claim 23, wherein the expansion and return ports
are disposed circumferentially around the conduit.
37.-41. (canceled)
42. The device of claim 22, further comprising a third lumen
extending toward the distal end of the conduit, and one or more
additional dehumidified air delivery ports at the distal end in
fluid communication with the third lumen.
43. The device of claim 22, further comprising a third lumen
extending towards the distal end of the conduit in fluid
communication with the return ports.
44.-59. (canceled)
60. A device according to claim 22, further comprising device to
monitor humidity of air delivered to a subject.
61. A device according to claim 22, further comprising a device to
monitor temperature of air delivered to a subject.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a Divisional of U.S. patent application
Ser. No. 13/751,617, filed Jan. 28, 2013, which is a
Continuation-in-Part of U.S. patent application Ser. No.
13/579,370, filed Jan. 9, 2013, now granted U.S. Pat. No.
9,629,746, issued Apr. 25, 2017, which is a 35 U.S.C. .sctn. 371
U.S. national entry of International Application PCT/US2011/025121,
having an international filing date of Feb. 16, 2011, which claims
the benefit of U.S. Provisional Application No. 61/305,038, filed
Feb. 16, 2010, and U.S. Provisional Application No. 61/315,218,
filed Mar. 18, 2010. This application also claims the benefit of
U.S. Provisional Application No. 61/590,844. The content of each of
the aforementioned applications is herein incorporated by reference
in their entirety.
BACKGROUND OF THE INVENTION
Field of the Invention
[0002] The invention relates generally to methods and devices for
removing heat, energy, and/or fluid from a living mammal. In
particular, this invention relates to a method and device for
controlled delivery of gas to the nasopharyngeal cavity, lungs or
other anatomical feature of a mammal. The invention also relates to
therapeutic methods for using the method and device to provide
cerebral cooling, systemic cooling, and neuroprotection via such
cooling. The invention further relates to methods for using the
methods and device to remove excess fluid from the body in cases of
cardiogenic shock and other conditions which result in the
accumulation of excess fluid. The invention additionally relates to
methods for removing energy from the body, for increasing metabolic
rate, and for promoting weight loss.
Background Information
[0003] Removal of heat, energy, and/or fluid from a body is a
proven therapeutic requirement for many critical and non-critical
health conditions. Such conditions include cardiac arrest,
refractory heart failure, stroke, sport or combat related
overheating, heat cramps, heat exhaustion, heat stroke, compromised
renal function, obesity, and many others. For each of these
conditions, there is a continuing need for non-invasive therapies
to remove heat, fluid and/or energy from the body.
[0004] Cardiac arrest (CA) is a leading cause of morbidity and
mortality in the developed world. Resuscitation is attempted in an
estimated 400,000 patients annually in the United States and 66 per
100,000 population every year in Europe.sup.1, 2. Recovery without
residual neurologic damage after cardiac arrest with global
cerebral ischemia is rare. Of the few that survive to hospital
discharge, >50% are left with permanent neurological
sequelae.sup.3, 4. After cardiac arrest with no blood flow for more
than five minutes, the generation of free radicals, during
reperfusion, together with other mediators, creates chemical
cascades that result in cerebral injury'. Several studies have
shown that moderate systemic hypothermia (30.degree. C.) or mild
hypothermia (34.degree. C.) markedly mitigates brain damage after
cardiac arrest in dogs.sup.6-8. Two well-conducted rand3mized
clinical trials demonstrated the benefit of cooling survivors of
witnessed CA who had ventricular fibrillation (VF) as the
presenting rhythm.sup.2-9. Based on these data, the American Heart
Association and the European Resuscitation Council recommend
therapeutic hypothermia (TH) in the management of unconscious
patients following CA.sup.4, 10.
[0005] Despite the strong experimental and clinical evidence, the
use of TH is at best sporadic, with less than 10% of the eligible
CA patients receiving hypothermia.sup.5, 11. Animal studies suggest
that cooling early after ROSC is associated with improved
neurological outcome and a delay in initiation of hypothermia is
associated with decreased benefif.sup.7, 12. One of the important
factors in rapid induction of TH is the unavailability of a
reliable, easy to implement method in the field that does not
interfere with resuscitation attempts. Current out-of-hospital
methods to induce TH include ice-cold saline IV, ice packs.sup.2,
cooling blankets.sup.12, and cooling helmets, which are ineffective
to induce hypothermia. As such, there is an enormous need for a
method to induce TH in the out-of-hospital setting that is
non-invasive, rapid, effective, and without major harmful side
effects.
[0006] The ability to induce hypothermia non-invasively and in a
timely fashion is of enormous clinical value not only in cardiac
arrest, but also in all threatened ischemic insults including
cerebrovascular ischemia, traumatic brain injury, spinal cord
injury, neonatal encephalopathy and coronary artery disease.sup.14.
In cardiac arrest alone, TH will save an additional 7,500 lives per
year with 50 patients treated per life saved.sup.2. Post-CA
patients receiving TH gain an average of 0.66 quality-adjusted life
years at an incremental cost of $31,254 due to the extended
hospital stay.sup.11, which has comparable cost-effectiveness per
quality-adjusted life year to many economically acceptable health
care interventions.
[0007] Investigators have tried cooling the body through the nasal
passages using non-compressed, low-flow air/oxygen and observed the
hypothermic effect, although the mechanism behind the effect was
not well understood.sup.21,22. For example, the RhinoChill.TM.
device achieves cooling by evaporating a coolant perfluorocarbon
(PFC) in the airway or by using a volatile gas to evaporate water
vapor introduced into the air to decrease the air temperature in
the nasal cavity.sup.22, 23. Evaporation of the coolant PFC in the
nose reportedly results in convective cooling of the brain and core
body temperature.
[0008] However, ambulatory hypothermia methods relying on direct
heat exchange using either cold perfusates (coolants) or surface
cooling by evaporation of a volatile substance can produce
excessively extreme local cooling of the exposed surfaces, at some
risk to the patient. As such, such active cooling therapies are to
be administered by specially trained medical technicians.
[0009] In conditions of cardiac stress, a patient will build up
excess water in the extremities. Presently, the primary way to
remove water from the body is via urination by the use of diuretic
drugs. This method can take a significant period of time, and may
not be useful especially in patients with compromised renal
conditions.
[0010] Additionally, there is a need for augmented body cooling in
cases of combat and sports related overheating due to exertion and
adverse ambient conditions.
[0011] Furthermore, there is a need to remove energy (calories)
from a body as a means to augment weight loss.
[0012] Thus, a need exists for a minimally or non-invasive method
to remove heat, fluid and/or energy without use of coolants or
volatile substances for instance, which preferably can be used in
non-medical settings, without supervision by specially trained
personnel.
SUMMARY OF THE INVENTION
[0013] The present invention provides a minimally or non-invasive
method and device to provide passive anatomical, systemic cooling,
fluid extraction, energy extraction, metabolic rate increase and/or
weight loss, by utilizing the nasal heat loss mechanism wherein
heat and fluid is lost intentionally by the body due to its natural
response to humidify and condition the inspired air.
[0014] As such, in one aspect, the invention provides a method of
passively cooling an anatomical feature in a mammal by controlled,
induced evaporation of a bodily fluid from a bodily
fluid-containing space or surface, such as a mucus containing-space
or surface in the mammal. The method includes delivering a dry
fluid (compressed or not) which does not include a coolant (i.e., a
refrigerant or chilled fluid) into or upon the bodily
fluid-containing space or surface to provide controlled evaporation
and transport (removal) of the bodily fluid upon contact with the
dry fluid. Such evaporation and transport of the bodily fluid
produces cooling of the anatomical feature and systemic cooling, as
well as body fluid elimination. In one embodiment, the fluid is a
gas.
[0015] According to the cooling aspect of the invention, the
invention provides methods for reducing overheating and providing
comforting and/or therapeutic cooling in cases of heat related
stress, including overheating resulting from sport and/or combat
activities, fever, heat exhaustion and heat stroke.
[0016] The invention also provides a method for removing excess
body fluids in cases where removal of fluids is useful in the
treatment of certain conditions including refractory heart failure,
in which the body retains fluid in extremities.
[0017] In cases where there is not a need to cool the body or
remove excess heat or fluid, the invention provides a method for
the extraction of fluid and energy, promoting weight loss.
[0018] In various embodiments, the gas is dehumidified prior to
delivery to the bodily fluid-containing space or surface for
cooling of the targeted anatomical feature. In various embodiments,
the fluid has a relative humidity before delivery to the mammal of
less than or equal to about 90, 80, 70, 60, 50, 40, 30, 20, or 10%.
In various embodiments, the gas is delivered at a flow rate of
greater than about 10 L/min, such as a flow rate of between about
20 and 200 L/min, 40 and 130 L/min, 20 and 80 L/min, or 40 and 500
L/min.
[0019] According to metabolic rate increase and weight loss
embodiments, system of the invention may be used overnight over
extended periods of time, and the flow rate is preferably set at a
lower range, for example between about 10 and 40 L/Min, to improve
long term tolerability.
[0020] Where cooling is not required or desired and in cases of
fluid extraction applications, the gas may be warmed to increase
fluid extraction. According to this embodiment, the gas may be
warmed to body temperature, or >30.degree. C., >40.degree. C.
or greater than >50.degree. C.
[0021] In various embodiments, the fluid is delivered to a bodily
fluid-containing surface or cavity, such as the nasal cavities
(nasopharynx and nostrils), oral cavity, lungs, trachea,
gastro-intestinal system, stomach, and urogenital cavity and mucus
surfaces. According to one cooling embodiment, the anatomical
feature is the brain or brain stem, and delivery of the fluid is
made to the nasal cavities. In one embodiment, the gas is delivered
for a duration to lower core body temperature of the mammal between
about 2 to 4.degree. C. In an especially preferred embodiment, the
mammal is a human.
[0022] Conveniently, the susceptibility of the invention to
practice with uncompressed fluid (such as ambient air) lends it to
use with relatively simple air delivery devices, such as
respiratory masks or nebulizers. The device may be portable and may
also be configured to optionally work via battery power. The
invention is therefore particularly well-suited to use in
ambulatory therapies, including emergency settings, combat
settings, sport settings, and even clinic and home-use settings. In
a particularly preferred embodiment, the gas is delivered via a
device of the present invention.
[0023] Accordingly, the present invention further provides a device
for cooling an anatomical feature in a mammal, providing systemic
cooling in a mammal, removing excess fluid from a mammal, raising
the metabolic rate of a mammal, and/or promoting weight loss in a
mammal, by evaporation of a fluid from a bodily fluid-containing
space or surface in the mammal. The device includes: a) a conduit
which includes a proximal end, a distal end, a first lumen
extending between the proximal and distal ends, and one or more
fluid delivery ports at the distal end in fluid communication with
the first lumen; and b) a fluid source in fluid communication with
the proximal end of the first lumen for supplying a dry fluid not
containing a coolant to the first lumen; wherein the device is
configured such that fluid flows distally along the first lumen
through the fluid delivery ports to contact the bodily
fluid-containing space or surface upon expansion of the fluid
through the fluid delivery ports. If the dry fluid is compressed, a
compressor may be provided to the fluid source; or the fluid may be
provided in pre-compressed condition; e.g., in a valved tank or
other canister.
[0024] In various embodiments, the device further includes: c) a
second lumen extending toward the distal end of the conduit; d) one
or more return ports at the distal end in fluid communication with
the second lumen; and e) an exhaust port in fluid communication
with the proximal end of the second lumen; wherein the device is
configured such that fluid flows distally along the first lumen
through the fluid delivery ports and reenters the second lumen
through the return ports.
[0025] In some embodiments, the device also further includes one or
more temperature sensors (for the fluid and/or the treated mammal),
pressure sensor and/or fluid flow regulator. In some embodiments
the device includes a third lumen extending toward the distal end
of the conduit, and one or more additional fluid delivery ports at
the distal end in fluid communication with the third lumen and/or
the exhaust ports. The device may be configured to be lightweight
and portable, and may be configured to operate via connection to
standard wall socket and/or optionally by onboard rechargeable
battery. The device may optionally include a disposable desiccant
cartridge and may be provided with optional inputs for receiving
air and/or other gases via an external tank.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Various features and advantages of the disclosure will
become more apparent by the following detailed description of
several embodiments thereof with reference to the attached
drawings, of which:
[0027] FIG. 1 illustrates a diagram of a cooling device and
methodology of the present invention, according to an
embodiment;
[0028] FIG. 2 illustrates a diagram of a portion of a cooling
device of the present invention, according to an embodiment;
[0029] FIG. 3 illustrates a diagram of a portion of a cooling
device of the present invention, according to an embodiment;
[0030] FIG. 4 illustrates a diagram of a portion of a cooling
device of the present invention, according to an embodiment;
[0031] FIG. 5 illustrates a diagram of a portion of a cooling
device of the present invention, according to one embodiment;
[0032] FIG. 6 illustrates a diagram of a cooling device and
methodology of the present invention, according to an
embodiment;
[0033] FIG. 7 illustrates a diagram of a portion of a cooling
device, according to an embodiment;
[0034] FIG. 8 illustrates a diagram of a cooling device and
methodology of the present invention, according to an
embodiment;
[0035] FIG. 9 illustrates a diagram of a cooling device and
methodology of the present invention, according to an
embodiment;
[0036] FIG. 10 illustrates a diagram of a portion of a cooling
device and methodology of the present invention, according to an
embodiment;
[0037] FIG. 11 is a graphical representation showing the core body
temperature (measured in the right atrium) (top) and brain
temperature (measured in lateral ventricles) (bottom) during 100
L/min flow of nasal dry air in an intubated adult pig;
[0038] FIG. 12 is a graphical plot showing the effects of airflow
rate on the change in brain temperature, shown from 20 L/min to 300
L/min; and
[0039] FIG. 13 is a histogram comparing the rate of brain cooling
using various TH techniques.
[0040] FIG. 14 is a graph showing the energy required by a mammal
to condition (heat and moisturize) inspired air to the temperature
and humidity appropriate for inhalation to the lungs.
[0041] FIG. 15 is a graph showing the energy required by a mammal
to condition inspired air at different inlet conditions.
[0042] FIG. 16 is a graph showing the water extraction rate
according to an embodiment of the present invention versus air flow
rate at different inlet conditions.
[0043] FIG. 17 is a representation of a device according to one
embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0044] The contents of all references cited herein are to be
considered to be incorporated within this disclosure by this
reference.
[0045] The nose in mammals has highly convoluted turbinates with
extensive vascularization with a subepithelial capillary system,
and a distensible, cavernous, vascular network.sup.15. The
turbinates enormously increase the surface area and are richly
vascular and capable of engorgement in response to environmental
stimuli, especially cold and dry air stimulation.sup.16, 17.
Unidirectional flow of ambient air through the nose results in a
65% increase in nasal mucosal blood flow, an effect that is
promptly mitigated by humidification and warming of the inspired
air.sup.17-19. Moreover, warm dry air results in significant
increase in upper airway blood flow as compared to cold dry air
hyperventilation, which is subsequently mitigated by humidifying
the air. Respiratory water loss also follows a similar paradigm
with a water loss of 0.66.+-.0.17 g H.sub.2O/min for cold dry air
ventilation and 0.90.+-.0.16 g H.sub.2O/min for warm dry air
hyperventilation for airflow rates of up to 20 L/min.sup.16. This
water loss by the body is in fact heat loss due to the high latent
heat of evaporation of water (2.27 kJ/g), which is provided by the
nasal blood flow. Unidirectional flow in the nostrils is associated
with significant dehydration with water lost during humidification
of the inspired air..sup.17 Experimental testing shows that the
rate of water loss by this process is directly associated with heat
loss by the body, making humidification an excellent way to extract
heat.
[0046] In contrast, evaporation of a coolant or volatile gas
introduced into the nose reduces evaporation of bodily fluids
present (and reduces related water loss). While cooling may result
from both evaporative processes, the former path to cooling is less
controllable than is cooling resulting from the body's intrinsic
response to induced water loss.
[0047] The present inventions are based in part on the observation
that anatomic and systemic cooling, including therapeutic
hypothermia, as well as fluid removal, metabolic rate increase, and
weight loss, may be achieved by evaporation of a fluid from a
bodily fluid-containing space or surface using high flow dry air
applied to the space. The invention is based on the physiological
evaporative response to dry fluid, such as gas flow. Introduction
of dry air into a bodily fluid-containing space or surface, such as
the nasal or nasopharynx cavity causes release of the bodily fluid
from membranes, whose subsequent evaporation produces vasodilation,
evaporative heat loss and cooling of blood. With regard to the
nasal cavity, during normal breathing, energy (via the
humidification process) is transferred into the inspired air before
entering the lungs. After the inhaled air cycles through the lungs,
some of the energy in the air is transferred back into the nasal
turbinates during exhalation. However, without being bound to a
particular theory, the present method and device bypasses the
transfer of energy back in to the nasal turbinates during
exhalation. As opposed to other techniques, the present inventions
do not utilize coolants, such as refrigerants or chilled fluids, to
achieve cooling, heat removal, fluid removal and/or metabolic rate
increase.
[0048] In contrast to other techniques where exposed surfaces are
actively cooled by applying a refrigerant or chilled material to
the surface, the present method relies on heat loss directly from
the vasculature providing circulation to the tissue of a bodily
fluid-containing space or surface with no significant change in
surface temperature. For example, the inventors have confirmed that
the temperature within the space defined by nostrils exposed to
high flow dry gas to nostrils is similar to the inspired air
temperature suggesting that the gas does not directly cool the
surface of the nasopharynx. This is advantageous over other
techniques since generation of extreme cold surface temperatures
can be associated with vasoconstriction and shunting of blood flow
away from the tissue undermining the effect of surface cooling
method. Additionally, without being bound by any particular theory,
warm high flow of warm dry air is associated with a greater degree
of cooling, an approach which is counterintuitive, but
physiologically plausible as warm dry air has been shown to
increase respiratory water loss, which then translates to heat
loss.
[0049] Before the present device and method are described, it is to
be understood that this invention is not limited to the particular
configuration and method described. It is also to be understood
that the terminology used herein is for purposes of describing
particular embodiments only, and is not intended to be limiting,
since the scope of the present invention will be limited only in
the appended claims.
[0050] As used in this specification and the appended claims, the
singular forms "a", "an", and "the" include plural references
unless the context clearly dictates otherwise. Thus, for example,
references to "the method" includes one or more methods, and/or
steps of the type described herein which will become apparent to
those persons skilled in the art upon reading this disclosure and
so forth.
[0051] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Although
any methods and materials similar or equivalent to those described
herein can be used in the practice or testing of the invention, the
preferred methods and materials are now described.
[0052] In one aspect, the present invention provides a non-invasive
method to induce TH to provide anatomical and/or systemic cooling.
As such, in one aspect, the invention provides a method of cooling
an anatomical feature in a mammal by evaporation of a dry fluid
from a bodily fluid-containing space or surface in the mammal.
[0053] As used herein, "absolute humidity" is used to refer to the
amount of water vapor in a gaseous mixture of gas and water vapor
as expressed by mass. "Relative humidity" is used to refer to the
amount of water vapor that exists in a gaseous mixture of gas and
water vapor as a function of its current state, for example
temperature. Essentially, relative humidity is a measure of the
amount of moisture in the air compared to what the air is capable
of holding at a given temperature. In various embodiments, the
relative humidity of the gas before being contacted with a bodily
fluid is less than or equal to about 90, 80, 70, 60, 50, 40, 30,
20, 10, 5 or 0%. In various embodiments, the relative humidity of
the gas after being contacted with a bodily fluid is greater than
or equal to about 0, 10, 20, 30, 40, 50, 60, 70, 80 or 90%.
[0054] As used herein, a "dry" fluid or gas is used to refer to a
fluid or gas that is unsaturated with water vapor or other liquid
vapor. In various embodiments, the dry gas has a relative humidity
of less than or equal to about 90, 80, 70, 60, 50, 40, 30, 20, 10,
5 or 0%.
[0055] As used herein, the term "fluid" refers to dry
(dehumidified) fluid which effectuates evaporation. As is
recognized by one in the art, all gases are fluids. Accordingly,
the term fluid is used interchangeably with the term gas.
[0056] In various embodiments, dry gas is used in the method and
device of the invention to achieve anatomical cooling, systemic
cooling, TH, excess fluid extraction, metabolic rate increase
and/or weight loss. Several types of gases are suitable for use
with the present invention. Such gases include, but are not limited
to air, N0.sub.2, C0.sub.2, O.sub.2, and inert gases, such as He,
Ar, and Xe, as well as combinations thereof. In related
embodiments, the gas may be an anesthetic, such as N.sub.20 or Xe,
or a gas which additionally may have neuroprotective properties and
systemic effects to promote systemic cooling, such as
vasodilation.
[0057] Dry fluids delivered according to the invention do not
include a coolant (and may be, but need not be, warmed). As used
herein, the term "coolant" includes volatile gases and may include
dry ice, liquid nitrogen chilled saline, water, anti-freeze
solution, refrigerants, such as fluorocarbons, chlorofluorocarbons
(CFCs), hydrochlorofluorocarbons (HCFCs), perfluorocarbons (PFCs),
R-134a (1,1,1,2 tetrafluoro ethane), Freon.TM., and other cooling
fluids or refrigerants, or a combination thereof. A coolant may
also be considered any fluid chilled to a temperature 10.degree. C.
or more below normal body temperature. For humans, a coolant would
thus be a fluid chilled to about 27, 26, 25, 24, 23, 22, 21, 20,
19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1,
0.degree. C. or less.
[0058] The dry fluid is provided to the bodily fluid-containing
space or surface according to the invention. Contact of the flowing
dry fluid with such bodily fluid, for example mucus, results in
evaporation and cooling of a targeted anatomical feature (i.e., one
to which the dry fluid is directly delivered, or which is in
circulatory communication with the delivery site for the dry fluid
into a bodily fluid-containing space or surface of the body) and/or
systemic cooling (more generalized hypothermia). The evaporation
results in fluid loss/elimination and the cooling is a result of
the heat transfer. Extended periods of such heat transfer, which
can also be characterized as heat loss, will eventually result in
an increased rate of metabolism in the same way that the body
reacts to cold.
[0059] In the normal respiratory process, inspired air is
conditioned prior to entering lungs. Air is heated to near body
temperature, and is fully humidified. During normal expiration
(normal respiration air volumes), moisture used to humidify
inspired air is recaptured by the nasal turbinates as a means to
conserve energy. FIG. 14 shows the energy required by a mammal to
condition inspired air to the temperature and humidity appropriate
for normal lung function at varying air flow rates. The lower,
black, line, shows the energy required to heat air inspired at
77.degree. F. to 86.degree. F.; the middle, blue, line shows the
energy required to moisturize air inspired at 50% relative humidity
to 100% relative humidity.
[0060] FIG. 15 shows the energy required by a mammal to condition
three different inspired air conditions to temperature and humidity
appropriate for normal lung function at varying flow rates. The
bottom, black, line shows the energy necessary to condition air
inspired at 90.degree. F. and 70% relative humidity. The middle,
blue, line shows the energy necessary to condition air inspired at
77.degree. F. and 50% relative humidity, and the red line shows the
energy necessary to condition air inspired at 35.degree. F. and 20%
relative humidity.
[0061] FIG. 16 shows the water extraction versus flow rate for
different inspired air conditions. The bottom, black, line shows
the water extraction rate versus air flow rate for air inspired at
90.degree. F. and 70% relative humidity. The middle, blue, line
shows the water extraction rate versus air flow rate for air
inspired at 77.degree. F. and 50% relative humidity, and the red
line shows the water extraction rate versus air flow rate for air
inspired at 35.degree. F. and 20% relative humidity.
[0062] The method may be performed utilizing a device of the
present invention. Accordingly, the present invention further
provides a device for 1) cooling an anatomical feature in a mammal,
and/or 2) systemic cooling of a mammal, and/or 3) fluid extraction
from a mammal, and/or 4) metabolic rate increase, and/or weight
loss, by evaporation of a fluid from a bodily fluid-containing
space or surface of the mammal. As depicted in FIGS. 1 and 2, the
device includes a conduit 10 and a fluid source 20. The conduit 10
has both proximal 30 and distal 40 ends along with a first lumen 50
extending between the proximal 30 and distal 40 ends, and one or
more fluid delivery ports 60 at the distal end in fluid
communication with the first lumen 50. The fluid source 20 is in
fluid communication with the proximal end 40 of the first lumen 30
for supplying a dry fluid 70 not containing a coolant to the first
lumen 30. As such, the device is configured such that fluid flows
distally along the first lumen 30 through the fluid delivery ports
60 to contact the bodily fluid-containing space or surface. If the
dry fluid is a compressed gas, delivery occurs upon expansion of
the fluid through the fluid delivery ports, e.g. the nasal
cavity.
[0063] In various embodiments, the device may further include
additional features that allow for the introduced fluid to be
exhausted from the bodily fluid-containing cavity. To facilitate
removal of the fluid, device further includes a second lumen 80
extending toward the distal end of the conduit 40. The second lumen
80 includes one or more return ports 90 at the distal end in fluid
communication with the second lumen 80. As such, fluid that is
introduced and expanded through the fluid delivery ports 60 may be
allowed to flow out of the bodily fluid-containing space into the
second lumen through the return ports via natural flow of the fluid
or by applying a suction or negative pressure to the proximal end
of the second lumen. The device further includes an exhaust port
(e.g. an exhaust manifold) in fluid communication with the proximal
end of the second lumen to expel or dissipate the fluid to which
suction or a vacuum may be applied. As such, the device is
configured such that fluid flows distally along the first lumen
through the fluid delivery ports and reenters the second lumen
through the return ports after contacting and evaporating fluid,
such as mucus within or on the space or surface.
[0064] As used herein in reference to optional embodiments, the
term "compressed" fluid or gas is used to refer to a fluid or gas
that is under greater pressure than atmospheric. Compression of a
dry fluid may optionally be employed to allow for its delivery at
low flow rates compared to those required to induce the same
evaporative response to a dry fluid at atmospheric pressure.
[0065] A state of compression may result from the gas being
pressurized into a static containment vessel, or may result by
mechanically forcing, e.g., via a fan or blower, the gas through a
conduit or port having reduced volume. For example, with reference
to FIGS. 2 and 3, a compressed gas may be one that is forced along
the first lumen 50 via a fan 100 through the fluid delivery ports.
The gas may also be passed through a flow regulator 110 to further
alter the pressure of the gas as it flows through fluid delivery
ports 60. One in the art would understand that compression of the
gas may be further regulated by the configuration and size of the
exhaust ports. For example, reducing the number and size of the
fluid delivery ports 60 reduces the pressure of the gas in the
first lumen 50.
[0066] In various embodiments, the pressure of the compressed gas,
if employed, is regulated above atmospheric pressure, for example
above about 10-15 psi. For example, the gas may be regulated to
about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80,
85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150
psia or greater. To assist in regulating the pressure of the
compressed gas, the fluid source 20 may be a compressed gas source.
Additionally, the device may further include one or more valves
disposed along the conduit 10 to regulate pressure and flow of the
gas.
[0067] As shown in FIG. 3, the device may further include a
dehumidifier 120 to assist in regulating the humidity of the
gas.
[0068] As discussed herein, the invention is based in part on the
physiological evaporative response to dry fluid, such as gas flow.
Warm high flow of warm dry gas has been shown herein to be
associated with a greater degree of cooling. As such, as shown in
FIG. 3, the device may further include a heat exchanger 130 to
regulate the temperature of the gas. As used herein, the term
"warm" refers to a temperature of room temperature or greater. As
such warm air may be greater than about 20, 21, 22, 23, 24, 25, 26,
27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40.degree. C.
or greater.
[0069] In one embodiment, delivery of cooler gas is envisioned
where a lower rate of evaporation is desired, for example when a
longer duration of therapy is desired. As such the gas or air may
be greater than about 0, 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,
20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36,
37, 38, 39 or 40.degree. C. In preferred embodiments of the
invention, however, the dry fluid will be at normal body
temperature (e.g., for humans, 37.degree. C.) or warmer to a
clinically acceptable temperature, with dry fluid at the ambient
environmental temperature being particularly suitable for
ambulatory settings, especially in emergency contexts.
[0070] Without being bound by a particular theory, the temperature
of the gas is likely less significant than other factors, such as
flow rate and relative humidity, since the specific heat capacity
of a gas is low.
[0071] Any configuration of fluid delivery ports, alone or in
combination with return ports is envisioned to achieve desired gas
flow to result influid elimination, anatomic or systemic cooling,
energy removal, metabolic rate adjustment and/or weight loss. As
shown in FIGS. 4, 5, and 7, fluid delivery ports may be configured
in a variety ways to achieve a desired gas flow, in part depending
of the shape of the bodily fluid-containing space or surface. FIG.
4 shows an embodiment in which the first lumen is bifurcated at the
distal end to produce a fork shaped tip having parallel rows of
fluid delivery ports 60. It is envisioned that the first lumen 50
may be split to provide any number of parallel (or non-parallel)
rows of fluid delivery ports, for example 2, 3, 4, 5, 6, 7, 8 or
greater rows. In alternative embodiments, it is envisioned that
multiple rows of fluid delivery ports may also be created by
including additional lumens as discussed further herein.
[0072] As shown in FIGS. 5 and 7, a desired gas flow may also be
achieved by particular configurations of fluid delivery ports 60 in
relation to return ports 90. FIG. 5 shows an embodiment having 3
distal lumen. Two lumen 200 deliver gas through fluid delivery
ports 60, while one lumen 210 includes a single return port 90. In
this configuration gas expands out of fluid delivery ports 60 into
or on a bodily fluid-containing space or surface and is directed
into lumen 210 through return port 90 via suction applied to lumen
210. FIG. 7 shows an embodiment having multiple return ports 90
disposed distal to the fluid delivery ports 60. In this
configuration gas expands out of fluid delivery ports 60 into or on
a bodily fluid-containing space or surface and is direct into lumen
210 through return ports 90 via suction applied to lumen 210.
[0073] The device may include a number of additional features to
assist in regulating gas flow and pressure to achieve fluid
elimination, anatomic or systemic cooling, energy removal,
metabolic rate adjustment and/or weight loss. As shown in FIG. 2,
the device may further include a temperature sensor 95 and/or
pressure sensor 96. Such features allow the device to include
dynamic feedback to control temperature, pressure and gas flow
through the device and thus within, for example the bodily
fluid-containing space to optimize evaporation of the bodily fluid,
such as mucus to achieve fluid elimination, anatomic or systemic
cooling, energy removal, metabolic rate adjustment and/or weight
loss. For example, the temperature of the gas as it exits through
the fluid delivery ports 60 may be regulated by controlling the
pressure of the gas as it exits, as well as regulation of the gas
flow by feedback provided by the temperature sensor 95. A
temperature sensor which regulates delivery of the dry fluid in a
feedback response based on the mammal's measured temperature (of
the body or at the site of the targeted anatomical feature) may
also be provided.
[0074] Pressure sensor 96 is placed at the distal tip to monitor
pressure and includes means, such as a pressure transducer to
adjust gas flow via feedback along with the temperature sensor 95.
Following decompression and expansion of the gas through fluid
delivery ports 60, the gas exits the bodily fluid-containing space
by means of lumen 80. The flow out through the lumen 80 may be
regulated by the feedback from the pressure sensor via a suction
apparatus in fluid connection with the proximal end of lumen
80.
[0075] As discussed throughout, the fluid flow may be regulated by
a number of features, alone or in combination, e.g., sensors, port
size and number, gas pressure, and the like. The invention may
utilize high flow of gas, which includes flow rates of between
about 20 and 200 L/min, 40 and 130 L/min, or 20 and 80 L/min. For
example, gas may be delivered at a flow rate of greater than about
10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 65, 70, 75, 80, 85, 90, 95,
100, 105, 110, 115, 120, 125, and 130 L/min. As discussed herein,
the flow rate may be varied throughout the duration of delivery to
maximize evaporation within or on the bodily fluid-containing space
or surface.
[0076] In various embodiments, the device may further include
additional lumens to facilitate additional configurations of the
expansion and return ports. As discussed above, multiple lumens may
be provided to deliver gas through multiple fluid delivery ports.
Similarly, multiple lumens may be provided to expel gas from the
bodily fluid-containing cavity through multiple return ports.
Various combinations are envisioned depending on the desired gas
flow.
[0077] The duration of treatment will vary depending on the desired
level of fluid elimination, anatomic or systemic cooling, energy
removal, metabolic rate adjustment and/or weight loss.
[0078] It has been established that the reduction in core
temperature is related to the flow rate and dryness of the gas,
wherein an increase in flow rate and decrease in dryness increases
the core cooling rate. As such, an appropriate technique for
determining the desired duration to provide cooling treatment is
determined by monitoring the core body temperature. Typically the
gas is delivered for a duration to lower core body temperature of
the mammal between about 2 to 4.degree. C. However, the core body
temperature may be lowered by longer delivery of gas. Additionally,
it will be understood that once reached, a specific core body
temperature may be maintained by adjusting the flow rate, pressure,
temperature and humidity of the gas.
[0079] Where the desired result is fluid elimination, the duration
of treatment may be determined by monitoring flow rate, temperature
and change in humidity level (from inlet to exhaust). Where the
desired result is energy removal/metabolic rate adjustment/weight
loss, the duration of treatment may be determined a similar
approach. In the case of metabolic rate adjustment to promote
weight loss, the invention may be used overnight over a longer
period of time. The gas flow rate may be set at a lower flow rate,
e.g., between 20 and 40 L/min, to improve tolerability. The therapy
can also be intermittently paused to allow the mucus-containing
space or surface to recover, if needed.
[0080] In various embodiments, the gas is delivered to a bodily
fluid-containing space or surface. Such spaces and surfaces may
include, but are not limited to the lungs, trachea, oral cavity,
nasopharynx, nostrils, gastro-intestinal system, stomach,
peritoneal cavity, skin and urinary bladder. In various
embodiments, the body fluid-containing space or surface is a
mucus-containing space or surface, for example, any space or
surface that secretes or includes mucus, such as mucosal membranes
or cells. For example, with reference to FIGS. 1 and 6, the bodily
fluid-containing space or surface is the nasal or pharynx cavity.
In this embodiment, the device in configured to be introduced into
the nasal cavity and may include any of the features as shown in
FIGS. 1-7. In this configuration, gas is expanded through the fluid
delivery ports and cooling is achieved in part due to the
physiological evaporative response to dry gas air flow.
Introduction of the dry air into the nasal cavity causes release of
bodily fluid, such as mucus from the mucus membranes, whose
subsequent evaporation produces vasodilation, evaporative heat loss
and cooling of the blood in the carotid arteries as well as
conductive cooling of the brain stem.
[0081] In various embodiments, one being where the bodily
fluid-containing space or surface is the nasal or pharynx cavity,
the return ports are configured such that air flow is
unidirectional from the expansion ports to the return ports to
avoid heat loss of the gas back to the body.
[0082] As such, the term "bodily fluid" may encompass a variety of
different fluid types. Such fluids may include, but are not limited
to mucus, saliva, gastric fluid, urine, sweat and the like.
[0083] Evaporative cooling may be achieved in or on a variety of
bodily fluid-containing spaces or surfaces. In one embodiment, the
device may be configured to deliver gas to the pulmonary bed of the
lungs to achieve cooling and neuroprotection, FIG. 8 shows an
embodiment of a device for use in delivering gas to the lungs
through the oral cavity. However, it is envisioned that the lungs
may also be accessed via the nasal cavity. Additionally, various
configurations are envisioned such as a forked conduit allowing for
independent delivery and expulsion of gas in each of the left and
right lungs. FIGS. 9 and 10 show embodiments in which the device is
configured to deliver gas to the stomach. As shown in FIG. 9, in
one embodiment, the fluid delivery ports are disposed proximal to
the return ports such that gas flows from the nasopharynx cavity to
the stomach. Other port configurations are envisioned such as
providing both expansion and return ports in the stomach
cavity.
[0084] In another embodiment, the device is configured to deliver
gas to the mouth or oral cavity. In this embodiment, the device may
be configured with or without return ports. When no return ports
are desired, the delivered gas is allowed to exit exhaust from the
mouth which may be mechanically held open.
[0085] In various embodiments, the device may include additional
features known in the art to assist in placement of the conduit
into the desired cavity. For example, the device may further
include one or more inflation balloons disposed along the conduit
which may be inflated by an appropriate inflation fluid provided by
one or more lumens incorporated into the conduit.
[0086] In various embodiments, the conduit may be incorporated into
a variety of conventional medical devices. For example, the conduit
may be incorporated into a respiratory mask or nebulizer for
delivery of air into the nasopharyngeal and/or pharyngeal regions
of the nasal cavity. Such devices may be adapted to provide ambient
air or another suitable dry fluid supplied in a kit. Alternatively,
the conduit may be incorporated into a cannula, catheter, nasal
pillow or the like depending on the location of the surface or
cavity being accessed.
[0087] In various embodiments, the method and device of the
invention are useful for rapid emergency use (e.g., cardiac arrest,
stroke, heat stroke, heat exhaustion, etc.) since the device and
method are easy to implement, non-invasive, non-toxic, effective,
and do not interfere with current standard of care. For example, in
one embodiment to treat stroke victims, the device may employ
ambient air drawn by a vacuum or other suction means through a
device having expansion and return ports introduced into the nasal
passage. In both a related or alternative embodiment, as discussed
herein, compressed dry gas from a compressed gas source may be
introduced into the device.
[0088] Although the invention has been described with reference to
the above example, it will be understood that modifications and
variations are encompassed within the spirit and scope of the
invention. Accordingly, the invention is limited only by the
following claims.
Example 1
Nasal Cooling in Porcine Subjects
[0089] This example illustrates the effect of high flow nasal dry
air on the cortical and core body temperature in intubated adult
pigs, modeling human responses.
Core Body and Brain Temperature During High Flow Dry Air in
Intubated Pigs:
[0090] Four adult male pigs (70 pound) were anesthetized and
intubated. Thermocouples were placed in the right atrium and the
lateral ventricles through a temporal burr hole. Compressed dry air
was delivered through the custom nasal cannula at 80 to 100 L/min
for 10 minutes. FIG. 11 shows simultaneous recordings of core
temperature from the right atrium (top) and the brain temperature
from the lateral cerebral ventricles (bottom). The brain
temperature decreased from 35.9.+-.0.3.degree. C. to
32.3.+-.0.4.degree. C. over 10 minutes. During the same time
period, the core body temperature decreased from
35.8.+-.0.7.degree. C. to 35.2.+-.0.4.degree. C. The brain
temperature promptly returned to baseline within 10.+-.1.3 minutes
of cessation of the airflow. For a given flow rate, the rate of
temperature change was similar within the same animal and among all
four animals.
[0091] Effect of Air Flow Rate on Brain Temperature:
[0092] In two adult pigs, the effect of airflow rate on the rate of
brain cooling was evaluated. FIG. 12 shows recorded mean
temperatures at various airflow rates tested.
[0093] At airflow rates used clinically (20 L/min), no appreciable
change was observed in the brain temperatures. Flow-rates of 150
L/min and 300 L/min were indistinguishable and flow rate of 100
L/min showed intermediate results. In both animals at flow rates of
>100 L/min, moderate brain hypothermia (<34.degree. C.) could
be achieved in approximately 10 minutes.
[0094] Core Body Hypothermia Using High Flow Dry Air: At higher
flow rates (150 L/min and 300 L/min), a progressive decrease in
core body temperature was observed. It is expected that that
prolonged exposure to high flow dry air will lead to core body
hypothermia. The brain temperature declined similar to prior
experiments and achieved a plateau temperature of
30.1.+-.0.4.degree. C., however, the body temperature continued to
decline and reached a minimal value of 31.8.+-.0.8.degree. C. over
30 minutes. Cessation of airflow resulted in a gradual incomplete
recovery of baseline temperature to 34.5.+-.0.8.degree. C.
(baseline 35.6.+-.0.6.degree. C.) for the brain and
35.1.+-.0.2.degree. C. (baseline 35.5.+-.0.8.degree. C.) for the
body over the next 30 minutes. No significant changes were observed
either in the blood pressure, heart rhythm or the heart rate in all
the four animals.
[0095] This example demonstrates the feasibility of the present
invention to reproducibly induce brain and core body hypothermia in
intubated pigs using high flow of a gas (air) through the nostrils.
The rate of hypothermia using this approach appears superior to
published cooling rates using other ambulatory hypothermia methods
and devices.sup.3 as shown in FIG. 13. FIG. 13 demonstrates that
high-flow dry air resulted in superior rates of brain cooling
compared with both nasal coolant perflurocarbon (PFC) using the
RhinoChill.TM. device or irrigation of ice cold saline in the
nasopharynx.
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