U.S. patent application number 15/093143 was filed with the patent office on 2016-10-13 for non-invasive systems, devices, and methods for selective brain cooling.
The applicant listed for this patent is NEUROSAVE, INC.. Invention is credited to Thomas Kreck, Seth Rodgers, Ian Sas.
Application Number | 20160296365 15/093143 |
Document ID | / |
Family ID | 47597820 |
Filed Date | 2016-10-13 |
United States Patent
Application |
20160296365 |
Kind Code |
A1 |
Kreck; Thomas ; et
al. |
October 13, 2016 |
NON-INVASIVE SYSTEMS, DEVICES, AND METHODS FOR SELECTIVE BRAIN
COOLING
Abstract
Methods, systems, and devices are disclosed for providing
selective and non-selective cooling and warming of a patient.
Multiple embodiments of devices are disclosed for performing rapid
induction and maintenance of therapeutic hypothermia either in a
hospital setting or in the field so that hypothermic treatment can
be quickly instituted before significant tissue damage occurs.
Methods are also disclosed for targeting brain cooling by
irrigating the upper airway, aerodigestive tract, and/or more
generalized cooling by irrigating the esophagus and/or stomach.
Inventors: |
Kreck; Thomas; (San
Francisco, CA) ; Rodgers; Seth; (San Francisco,
CA) ; Sas; Ian; (San Francisco, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NEUROSAVE, INC. |
San Francisco |
CA |
US |
|
|
Family ID: |
47597820 |
Appl. No.: |
15/093143 |
Filed: |
April 7, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13558108 |
Jul 25, 2012 |
9320644 |
|
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15093143 |
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61511409 |
Jul 25, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 16/0436 20140204;
A61F 7/007 20130101; A61M 16/0438 20140204; A61M 19/00 20130101;
A61F 2007/0071 20130101; A61F 2007/0086 20130101; A61M 16/0495
20140204; A61F 7/12 20130101; A61F 2007/0095 20130101; A61F
2007/0288 20130101; A61M 16/0409 20140204; A61M 16/0479 20140204;
A61F 2007/0088 20130101; A61M 16/04 20130101; A61F 2007/0063
20130101; A61F 2007/0091 20130101; A61M 16/0459 20140204; A61M
2205/3606 20130101; A61M 16/0475 20140204; A61M 2210/0618 20130101;
A61F 2007/0002 20130101; A61M 2205/3331 20130101 |
International
Class: |
A61F 7/12 20060101
A61F007/12; A61M 19/00 20060101 A61M019/00; A61M 16/04 20060101
A61M016/04; A61F 7/00 20060101 A61F007/00 |
Claims
1. An apparatus for selective and non-invasive cooling of the brain
in intubated patients comprising: at least one nasal catheter sized
to be introduced through the nostrils of a patient; at least one
multi-lumen esophageal catheter sized to be inserted into the
esophagus of the patient, the esophageal catheter having a distal
end and a proximal end, the distal end configured to extend past
the aortic arch of the patient, the esophageal catheter comprising
a first lumen, a second lumen, and a third lumen, the first lumen
of the esophageal catheter extending from the proximal end to the
distal end to provide access to the stomach when the esophageal
catheter is disposed in the esophagus of a patient, the second
lumen of the esophageal catheter extending from the proximal end
and terminating inside a first esophageal inflatable member near
the distal end of the esophageal catheter, and the third lumen of
the esophageal catheter extending from the proximal end to a port
located proximal to the first esophageal inflatable member.
2. The apparatus of claim 1, where the at least one multi-lumen
tracheal catheter further comprises: a third lumen extending from
the proximal end of the catheter to a port located proximal to the
first tracheal inflatable member.
3. The apparatus of claim 1, where the esophageal catheter further
comprises a fourth lumen, the fourth lumen of the esophageal
catheter extending from the proximal end and terminating inside a
second esophageal inflatable member near the distal end of the
esophageal catheter.
4. The apparatus of claim 3, where the esophageal catheter further
comprises a port positioned between the first and second esophageal
inflatable members.
5. The apparatus of claim 1, where the tracheal catheter further
comprises a fourth lumen, the fourth lumen of the tracheal catheter
extending from the proximal end and terminating inside a second
tracheal inflatable member near the distal end of the tracheal
catheter.
6. The apparatus of claim 5, where the tracheal catheter further
comprises a port positioned between the first and second tracheal
inflatable members.
7. The apparatus of claim 1, further comprising at least one oral
catheter sized to be received in the oral cavity, oropharynx, or
hypopharynx of the patient.
8-9. (canceled)
10. The apparatus of claim 8, further comprising a filter module
positioned between the recirculation reservoir and the oral
catheter.
11. The apparatus of claim 9, where the discard location comprises
a waste reservoir, the waste reservoir having a capacity of between
1 and 20 liters and being maintained at or below atmospheric
pressure.
12. (canceled)
13. The apparatus of claim 12, where the waste reservoir includes a
vent that is movable between an open and a closed position.
14. (canceled)
15. The apparatus of claim 14, where the cooling unit is
reusable.
16. (canceled)
17. The apparatus of claim 14, wherein the cooling unit is in
thermal contact but not fluidic contact with the at least one heat
exchanger.
18. (canceled)
19. The apparatus of claim 14, further comprising at least one a
temperature monitoring device configured to obtain temperature
information and a temperature display configured to display the
temperature information.
20-21. (canceled)
22. The apparatus of claim 21, where the control unit is configured
to receive a target temperature and turn on, turn off, or vary the
speed of the at least one pump to adjust a temperature obtained by
the temperature monitoring device in consideration of the target
temperature.
23. The apparatus of claim 21, where the control unit is configured
to receive a target flow rate and one or more flow meters are
provided to one or more of the nasal catheter, the esophageal
catheter, and the tracheal catheter entering the patient and/or one
or more catheters leaving the patient, the control unit being
configured to adjust a flow rate based on the target flow rate and
information obtained by the one or more flow meters.
24-25. (canceled)
26. The apparatus of claim 25, where an additional pump is used to
drive fluid from the patient into a waste reservoir or a
recirculation reservoir.
27. (canceled)
28. The apparatus of claim 1, further comprising a head warming
member, the head warming member comprising a cap or a device
configured to deliver thermal energy to the head.
29. The apparatus of claim 1, further comprising a catchment under
portions of the neck and/or head that collects fluid that leaves
the body via the mouth or nose.
30-31. (canceled)
32. The apparatus of claim 1, further comprising one or more
surface warming devices, where the one or more warming devices is
configured to be heated by one or more of warm air, warm fluid,
thermal radiation, and resistive heating.
33-61. (canceled)
62. A method for cooling the brain, comprising: directing a
non-nebulized free flowing fluid through a plurality of catheters
into the aerodigestive tract of a patient; removing the fluid from
the aerodigestive tract of the patient through at least one of the
plurality of catheters; and recirculating the fluid through the
plurality of catheters until reaching a brain to body core
temperature gradient of at least 3.degree. C.
63-183. (canceled)
184. The method of claim 62, further comprising: positioning an
external warming device on the patient's body to maintain body core
temperature higher than a temperature of the brain.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 13/558,108, filed Jul. 25, 2012 and issued as
U.S. Pat. No. 9,320,644, which claims priority to U.S. Provisional
Patent Application No. 61/511,409, filed Jul. 25, 2011, which are
incorporated herein by reference in their entirety.
BACKGROUND
[0002] 1. Field of the Invention
[0003] A device, system, and method are disclosed for controlling
and/or regulating temperatures of the brain and/or body in a
subject.
[0004] 2. Description of Related Art
[0005] Brain injury is common, devastating, and often very
expensive to treat. Management of patient temperature by either
induction of hypothermia or aggressive treatment of fever has been
recommended by the American Heart Association (AHA) as the standard
of care for cardiac arrest. Brain temperature management has also
been used to treat birth-related cerebral damage and has been FDA
approved therapy during cardiac and neurosurgery. Temperature
management has been investigated for a variety of central nervous
system conditions, including stroke, mechanical brain trauma, and
spinal cord injury. A variety of devices have been proposed for
therapeutic organ cooling and in particular therapeutic cooling of
the brain. Such devices generally fall into one of two broad
categories: systemic devices and selective devices.
[0006] Systemic devices are widely used today, but selective
devices offer compelling advantages. Selective cooling enables the
creation of a temperature gradient between the brain and the body
core, which can reduce complications associated with body core
cooling, resulting in improved patient safety and enabling deep
cooling of the brain tissue to achieve neuro-protection.
[0007] In general, a high degree of selectivity in temperature
management has required a high, and generally undesirable, degree
of invasiveness. Surgically invasive devices, such as intravascular
devices, often focus on cooling the blood supply to a target area
and warming the returning blood supply to prevent cooling of the
body core. Intravascular systems and other similarly invasive
devices, however, may not be suitable for rapid deployment because
they require intervention by a surgeon. A further limitation of
catheter-based devices is that they require surgical invasion of a
major blood vessel, introducing risk of infection, bleeding,
thrombosis, rupture of the blood vessel, dissection of the blood
vessel wall and introduction or dislodging debris in the
vasculature. These risks are doubled when an intravascular warming
catheter is introduced to re-warm blood flow returning from the
cooled organ(s).
[0008] Other selective, brain focused, non-invasive cooling devices
require nebulized fluids that undergo a phase change (evaporation)
to maximize a rate of heat transfer from the body. An example of
this method is described for example, in U.S. Pat. No. 7,837,722 to
Barbut et al. Drawbacks of this approach include exposure of the
patient to fluorocarbon coolant (if used as a free flowing liquid),
exposure of bystanders to fluorocarbon coolant, and the formation
of entrained debris that is difficult to recapture as the coolant
leaves the patient. Also, this approach appears to yield a
relatively slow cooling rate in human trials, about 2.degree. C.
per hour and to our knowledge, a shallow average depth of cooling
of <4.degree. C. steady state reduction in brain
temperature.
[0009] Another selective device is described in U.S. Pat. No.
7,189,253 to Lunderqvist et al. The Lunderqvist devices introduce
fluid filled balloons into the nasal cavity and cool the cavity by
recirculating cold fluid. These devices control brain temperature
by adjusting the temperature of the cooling fluid based on
measurement of tympanic membrane temperature. Drawbacks of this
approach include a reduction in heat transfer rate due to a
reduction in surface area exploited (e.g., the surface area of the
sinuses is excluded and the air in the sinuses acts as a barrier to
heat transfer) and the heat transfer resistance of the balloon
itself. In addition, trauma to the nasal cavity is possible during
balloon expansion in the nasal cavity, which is accomplished by
restricting fluid flow from the balloon to increase a fluid
pressure within the balloon.
[0010] These approaches are limited in that they exploit the nasal
cavity only, resulting in in a lower heat transfer rate than one
which includes, for example, the remainder of the pharynx and the
esophagus. For example, the surface area used for heat transfer is
greater when the pharynx and esophagus are included. As another
example, the heat transfer rate through the perivascular tissue is
slow relative to the flow rate of blood rising in the carotid and
vertebral arteries. That is to say, the blood flowing in the large
arteries of the chest, neck, and head will not thermally
equilibrate with the tissue surrounding the arteries during active
temperature manipulation, except in circumstances of severely
reduced blood flow. The long cold zone of a combined esophageal,
pharyngeal, and nasal approach means an enhanced residence time in
the cold zone for the blood and thus a greater degree of
equilibration and cooling.
[0011] Other conventional approaches utilize balloon-based devices,
such as those disclosed by Takeda in U.S. Patent Publication Nos.
2008/0086186 and 2009/0177258. Such contained use of fluids
generally does not, for example, provide good surface contact with
the tissues of the airway or stomach, reducing heat transfer. In
addition, such methods can make it difficult to provide access to
adjacent areas of the body to promote respiration and/or allow the
passage of liquids or gases.
[0012] If warming and cooling are used together to create a
brain-body temperature gradient, it can be beneficial to use some
type of control system to coordinate the warming and cooling
activities. Conventional systems for providing temperature controls
to separately cool and warm portions of a patient, like that
disclosed by Lennox in U.S. Patent Publication No. 2003/0130651, do
not have integrated control systems and, as a result, neither
temperature control is aware of the action of the other except via
measurements of patient temperature. Accordingly, such systems,
with their non-integrated controls and reliance on single point
measurements of brain and body temperature, respectively, cannot
optimally account for time lags between actions in the brain
cooling system and responses in body temperature, among other
things.
SUMMARY
[0013] The slow rate of cooling and/or delays in initial treatment,
for example, in conventional therapeutic hypothermia devices and
methods can limit the effectiveness of those systems in preserving
tissue function (e.g., such as neurological function) following
hypoxia, myocardial function following myocardial infarction,
stroke, and/or other types of function following inflammation or
injury. Conventional systems also have suffered from difficulties
in focusing cooling on the desired target organs without incurring
cooling-related complications in the rest of the body. At least
some of these disadvantages are addressed by the systems and method
disclosed herein, resulting in systems and methods that permit more
rapid and/or deeper selective therapeutic hypothermia, among other
things.
[0014] In one embodiment, a method for selectively and
non-invasively cooling the brain includes introducing an irrigating
fluid into a patient's aerodigestive tract, monitoring a first
temperature of the patient's body, setting a target temperature
that is different from the first temperature, and changing the rate
of flow of the irrigating fluid to bring the first temperature
closer to the target temperature. The method can include changing
the rate of flow (e.g., intermittently starting and stopping the
flow) of irrigating fluid to the patient's aerodigestive tract, as
needed, in response to a difference between the first temperature
and the target temperature.
[0015] In some disclosed embodiments, the cooling can be targeted
to the brain (for example, to preserve neurological function
following a stroke, brain injury, myocardial infarction, or episode
of cardiac arrest) or more generally to the entire body (for
example, to control generalized inflammation or injury to non-brain
structures, such as the spinal cord and/or myocardium).
[0016] In other disclosed embodiments, the improved systems for
inducing rapid hypothermia include cooling a region of the
aerodigestive tract for rapid selective brain cooling. This rapid
cooling can permit the method to be used more effectively in urgent
situations so that effective cooling can be induced prior to
completion of irreversible tissue damage. Following induction, the
method is also capable of effectively maintaining cooling for
sustained periods of time to provide maximal therapeutic benefit.
Variations of the method can achieve targeted or selective cooling
of the brain, or less selective cooling of both the brain and the
body, as required by clinical conditions.
[0017] In other embodiments, an apparatus for selective and
non-invasive cooling of the brain is provided. The apparatus can
include at least one nasal catheters (e.g., sized to be introduced
through the nostrils of a patient), at least one esophageal
catheters (e.g., multi-lumen esophageal catheters sized to be
inserted into the esophagus of the patient), and at least one
tracheal catheter (e.g., at least one multi-lumen tracheal catheter
sized to be inserted into the trachea of the patient). The
esophageal catheter can have a distal end and a proximal end, with
the distal end configured to extend past the aortic arch of the
patient when the esophageal catheter is disposed in the esophagus
of a patient. The esophageal catheter can include a first lumen, a
second lumen, and/or a third lumen (and in some embodiments, as
discussed below, a fourth lumen), with the first lumen of the
esophageal catheter extending, for example, from the proximal end
to the distal end to provide access to the stomach when the
esophageal catheter is disposed in the esophagus of a patient, the
second lumen of the esophageal catheter extending, for example,
from the proximal end and terminating inside a first esophageal
inflatable member near the distal end of the esophageal catheter,
and the third lumen of the esophageal catheter extending, for
example, from the proximal end to at least one port (e.g., one or
more ports) located proximal to the first esophageal inflatable
member. The tracheal catheter can include a first lumen, a second
lumen, and/or a third lumen (and in some embodiments, as discussed
below, a fourth lumen), with the first lumen of the tracheal
catheter extending, for example, from the proximal end to the
distal end to provide access to the lungs to allow the passage of
air into and out of the lungs when the tracheal catheter is
disposed in the trachea of a patient, the second lumen of the
tracheal catheter extending, for example, from the proximal end and
terminating inside a first tracheal inflatable member near the
distal end of the tracheal catheter, and the third lumen of the
tracheal catheter extending, for example, from the proximal end to
at least one port (e.g., one or more ports) located proximal to the
first tracheal inflatable member. In some embodiments, as discussed
below, tracheal and/or esophageal inflatable members can be
inflated with fluid and/or gases. In some embodiments, tracheal
and/or esophageal inflatable members can comprise at least one
pressure sensor configured to detect at least one of a pressure
within the inflatable member and a pressure exerted by the
inflatable member on tissue. In some embodiments, the apparatus
further comprises a base unit coupled to at least one of the
tracheal and the esophageal catheter and configured to regulate
pressure in the inflatable members. In some embodiments, the base
unit can be configured to alert a user when a threshold pressure is
met or exceeded (e.g., within the inflatable member and/or due to
surrounding tissue). Catheters in the present invention can
comprise a circular or a non-circular cross-section.
[0018] In other embodiments, the present apparatuses comprise an
apparatus for cooling at least one of the brain and the spinal
column, where the apparatus is configured to direct free flowing
fluid (e.g., non-nebulized) into an aerodigestive tract of a
patient, remove the fluid from the aerodigestive tract of the
patient, and recirculate the fluid into the aerodigestive tract
until reaching at least one of a target brain to body core
temperature gradient (e.g., at least 3.degree. C., 4.degree. C.,
5.degree. C., 6.degree. C., 7.degree. C., 8.degree. C., 9.degree.
C., 10.degree. C., 11.degree. C., 12.degree. C., 13.degree. C., or,
for example, from 3.degree. C. to 25.degree. C., 4.degree. C. to
12.degree. C., 10 to 12.degree. C., etc.) and a target spinal
column to body core temperature gradient (e.g., at least 3.degree.
C., 4.degree. C., 5.degree. C., 6.degree. C., 7.degree. C.,
8.degree. C., 9.degree. C., 10.degree. C., 11.degree. C.,
12.degree. C., 13.degree. C., or, for example, from 3.degree. C. to
25.degree. C., 4.degree. C. to 12.degree. C., 10 to 12.degree. C.,
etc.).
[0019] In another embodiment, a method for selective and
non-invasively cooling the brain is provided. The method can
include directing a free flowing fluid (e.g., non-nebulized) into a
nasopharynx, oropharynx, hypopharanx, and/or esophagus of a
patient, with the fluid being introduced into the nose, mouth,
and/or esophagus of the patient through a plurality of catheters.
The fluid can be directed out of the nasopharynx, oropharynx,
hypopharanx, and esophagus of the patient through one or more of
the plurality of catheters. The fluid can be recirculated and
redirected back into the nasopharynx, oropharynx, hypopharanx, and
esophagus of the patient. One or more of the cooling depth,
duration, power, and/or incoming fluid temperature can be
controlled based on measurements obtained from temperature inputs
from the body of the patient outside of the patient's brain.
[0020] In another embodiment, a method for preventing ventilator
associated pneumonia is provided. The method can include (a)
placing a tracheal catheter with a tracheal inflatable cuff at a
distal end of the tracheal catheter into the patient, (b) placing
an esophageal catheter with an esophageal inflatable cuff at a
distal end of the esophageal catheter into the patient, (c)
introducing a free flowing non-nebulized cold non-toxic irrigation
liquid into the aerodigestive tract with the cold irrigation liquid
substantially filling and directly contacting the walls of the
aerodigestive tract, and (d) inflating the tracheal inflatable cuff
and the esophageal inflatable cuff (e.g., with gas or liquid) to
restrict the flow of liquid in the patient to above a level of the
trachea and the stomach to achieve selective targeted cooling of
the brain.
[0021] In some disclosed embodiments, organ hypothermia is induced
by introducing a flow of non-nebulized cold, biologically
compatible irrigation liquid into the aerodigestive tract--but not
the lungs--of the subject so that the cold irrigation liquid
substantially fills and directly contacts the walls of the
aerodigestive tract to achieve rapid and effective heat exchange
over the large and irregular surface of the tract that the liquid
contacts. The cold irrigation liquid can be maintained at a
temperature of, for example, -30.degree. C. to 20.degree. C. The
liquid is allowed to flow in a coherent large volume mass through
the aerodigestive tract and along the exposed irregular surface of
the aerodigestive tract. In some embodiments, a flow of liquid is
also directed externally against the head of the subject (such as
the face and/or scalp) to further accelerate cooling. The head of
the subject may be at least partially immersed in cold liquid that
is agitated to apply flow for convective heat transfer. As another
example, a flow of a cold liquid can be directed toward the head of
the subject from a liquid flow tube even when the head is not
immersed in the cool liquid.
[0022] In one embodiment of the present methods, the irrigation
liquid is introduced into the aerodigestive tract by placing
multi-lumen catheters in the aerodigestive tract and flowing liquid
through the catheters into the aerodigestive tract. The catheters
in some examples are placed in the aerodigestive tract to introduce
the liquid only above the level of the trachea and esophagus to
achieve selective targeted cooling of the brain by primarily
cooling the structures near the brain and in contact with blood
vessels that supply blood to the brain.
[0023] In other examples, the catheters are placed to introduce the
liquid into the esophagus and/or stomach to achieve non-selective
organ cooling by bringing the liquid into contact with the
insulated structures of the mediastinum through which venous blood
returns to the heart. The insulated anatomic chamber provided by
the mediastinum, in combination with the high flow of cooling
liquid, permits excellent heat exchange with the circulating blood
to achieve the desired rapid cooling effect in a manner that is
less brain specific. In addition to the placement of catheters in
the esophagus and stomach, one or more catheters can also be placed
to introduce the flow of liquid into the upper aerodigestive tract
structures above the level of the esophagus to provide additional
or maximal cooling. For example, the catheters are placed with
their introduction ports or tips in the nasal cavity, oral cavity,
and/or hypopharynx (and preferably all three). In other
embodiments, the catheters have multiple lumens and/or multiple
ports to introduce the cooling liquid at multiple points along the
length of the catheters to increase the fluid flows outside of the
catheter that have been found to be effective in the rapid
protective induction of therapeutic hypothermia.
[0024] A subject can also be intubated with an endotracheal tube
having a cuff on the tube so that the cuff can be inflated (e.g.,
with gas, liquid, etc.) to inhibit entry of the irrigation liquid
into the lungs. In addition, a tube with an inflatable balloon can
be placed in the esophagus, and the balloon can be inflated (e.g.,
with gas, liquid, etc.) to substantially inhibit flow of liquid out
of the upper airway into the lower esophagus and stomach. Isolating
the gastrointestinal tract (including the lower esophagus (e.g.,
substantially below the aortic arch)) from the flow of cold liquid
in the upper airway helps direct the cooling effect to the upper
airway and the structures (including blood vessels) that are in
heat transferring proximity with the cold liquid.
[0025] To help achieve and maintain rapid and effective cooling of
the desired anatomic structures, it can be useful to provide a
sufficient reservoir of pre-cooled liquid for introduction
internally into the aerodigestive tract and/or externally against
the head. An external reservoir of irrigation liquid is provided
that supplies a sufficient volume of cool liquid at the selected
flow rate. In some embodiments, the reservoir is also a container
in which the head is completely or partially immersed.
Alternatively, the reservoir partially or completely surrounds a
receptacle in which the head is placed, and the receptacle collects
cooling liquid that flows out of the mouth and/or nose after it has
circulated within the aerodigestive tract outside of the irrigation
catheters. In other embodiments, the reservoir is placed in a back
support that also contacts the back and optionally cools the body
and structures of the back, such as the spinal cord. These and
other embodiments can be incorporated into devices that are or can
be attached to (or roll in tandem with) a stretcher so that the
hypothermia therapy can be administered to a patient in
transit.
[0026] The liquid that is introduced into the aerodigestive tract
can leave the aerodigestive tract by flowing out of the mouth
and/or nose of the subject to return to the external reservoir. The
return of the liquid can be passive, and not contained in a suction
tube, so that the cool return liquid flows along the length of at
least the upper airway or along the entire aerodigestive tract to
intimately contact the entire irregular surface of that tract. In
some embodiments, the aerodigestive tract--other than the lungs--is
substantially filled with the cooling liquid. Passive return of the
liquid can help avoid traumatic damage to the aerodigestive tract
that could occur if a return lumen is occluded in a system that
requires flow through such a circuit for removal. Liquid that flows
out of the mouth and nose of the subject can return passively to
the reservoir to be cooled, or circulated externally of the
reservoir for cooling. In other embodiments, the external reservoir
is a container in which at least part of the head is contained, or
over which the head is positioned, to collect the liquid that flows
out of the mouth and/or nose of the subject by gravity-assisted
flow of the liquid. However, in other embodiments, as described in
detail throughout this application, fluid can be actively removed
from the aerodigestive tract (e.g., by a suction device through at
least one of a plurality of catheters.
[0027] In some embodiments of the present methods, the liquid
reservoir is a neck support on which the neck of the subject is
positioned with the neck tilted backwards (extended) to help
protect the airway of the subject and promote the flow of liquids
through the aerodigestive tract (and not the lungs). In embodiments
in which the neck is extended, the head may be tilted back into a
container of cool liquid to partially, substantially, or completely
immerse the head in the cold liquid. Alternatively, the liquid
reservoir is a back and neck support that helps stabilize the spine
(for example, in cases of possible spinal injury). The support
itself may be hollow and contain the reservoir of cold liquid, or
the support may be a body supporting platform suspended over a tub
of cold water. For example, a tub can be large enough to receive a
body that is suspended above it, and in which ice or other cold
items can be placed along with the supply of cooling liquid. In
other examples, the reservoir has 1-50 liters of cool liquid in it,
or liquid to be cooled. The volume of cool liquid in the reservoir
can vary depending on the clinical circumstances. For example,
smaller volumes (1-20 L) may be preferred outside of an inpatient
setting (for example, in an ambulance), but larger volumes (e.g.,
greater than 20, 30, or 40 L) can be used for inpatient
settings.
[0028] In some embodiments, a method can comprise directing a free
flowing fluid (e.g., non-nebulized) into the aerodigestive tract of
a patient (e.g., through a plurality of catheters), removing the
fluid from the aerodigestive tract of the patient (e.g., through at
least one of the plurality of catheters), and recirculating the
fluid into the aerodigestive tract (e.g., through a plurality of
catheters) until reaching a target brain to body core temperature
gradient (e.g., at least 3.degree. C., 4.degree. C., 5.degree. C.,
6.degree. C., 7.degree. C., 8.degree. C., 9.degree. C., 10.degree.
C., 11.degree. C., 12.degree. C., 13.degree. C., or, for example,
from 3.degree. C. to 25.degree. C., 4.degree. C. to 12.degree. C.,
10 to 12.degree. C., etc.) and/or a target spinal column to body
core temperature gradient (e.g., at least 3.degree. C., 4.degree.
C., 5.degree. C., 6.degree. C., 7.degree. C., 8.degree. C.,
9.degree. C., 10.degree. C., 11.degree. C., 12.degree. C.,
13.degree. C., or, for example, from 3.degree. C. to 25.degree. C.,
4.degree. C. to 12.degree. C., 10 to 12.degree. C., etc.). In some
embodiments, the methods are configured to maintain a target brain
to body core temperature gradient and/or a target spinal column to
body core temperature gradient at a substantially constant gradient
for at least 1 hour, at least 4 hours, at least 12 hours, at least
24 hours, and/or from 1 to 12 hours. In other embodiments, the
fluid can comprise various additives, such as, for example,
electrolytes, antibacterial agents, propylene glycol, mucosal
protectants, and/or additives to make the fluid hypertonic. In some
embodiments, no cooling procedures are directed to the exterior of
the patient's head.
[0029] In some embodiments, a method can further comprise
activating a warming device to warm at least a portion of a
patient, directing a free flowing fluid (e.g., non-nebulized) into
the aerodigestive tract of the patient (e.g., through a plurality
of catheters), removing the fluid from the aerodigestive tract of
the patient (e.g., through at least one of the plurality of
catheters), and recirculating the fluid into the aerodigestive
tract of the patient (e.g., through the plurality of catheters). In
such embodiments, the warming device can comprise, for example,
warming blankets, hot air blankets, water blankets, and/or warming
bulbs. In some embodiments, the warming device can be disposed in
contact with a patient's head, in contact with the palms of a
patient's hands, in contact with the soles of a patient's feet, in
proximity to at least one of a patient's veins, and/or the like.
Further, warmed air can be passed into a patient's lung (e.g.,
through at least one of the plurality of catheters).
[0030] In other embodiments, the present methods can comprise
reducing blood flow to a patient's brain, directing a free flowing
fluid (e.g., non-nebulized) into the aerodigestive tract of the
patient (e.g., through a plurality of catheters), removing the
fluid from the aerodigestive tract of the patient (e.g., through at
least one of the plurality of catheters), and recirculating the
fluid into the aerodigestive tract of the patient (e.g., through
the plurality of catheters). Reducing blood flow to a patient's
brain can comprise, for example, sedating the patient, decreasing
the patient's blood pressure, administering barbiturates to the
patient (e.g., thiopental, phenobarbital, pentobarbital,
methohexital, etc.), administering propofol to the patient,
administering benzodiazepines to the patient, administering
lidocaine to the patient, administering etomidate to the patient,
administering caffeine to the patient, administering alcohol to the
patient, administering narcotics to the patient, administering
cocaine to the patient, administering beta-blockers to the patient
(e.g., labetalol), administering anti-migraine medications to the
patient (e.g., triptans, ergotamines, etc.), administering
clonidine to the patient, and/or administering vasoconstrictors to
the patient (e.g., phenylephrine). In other embodiments, reducing
blood flow to a patient's brain can comprise warming the exterior
of the patient's head, warming the patient's skin, reducing the
brain's metabolism, shunting blood to the body core away from the
brain, increasing jugular vein pressure, and/or inducing temporary
hyperventilation.
[0031] In some embodiments, the present methods comprise directing
a free flowing fluid (e.g., non-nebulized) into the aerodigestive
tract of the patient (e.g., a plurality of catheters), removing the
fluid from the aerodigestive tract of the patient (e.g., through at
least one of the plurality of catheters), monitoring a temperature
of at least one of patient's brain and the patient's body core, and
recirculating the fluid into the aerodigestive tract (e.g., through
the plurality of catheters) until a target temperature is reached.
In some embodiments, monitoring a temperature of a patient's brain
can comprise disposing a bolt comprising a temperature sensor in
the patient's brain, administering a magnetic resonance imaging
procedure to the patient, and/or inserting a temperature sensor
intravenously in the jugular and positioning the temperature sensor
near the brain.
[0032] This specification also discloses multiple devices for
carrying out the methods of inducing organ cooling in a subject. In
one example, a head receptacle is adapted for receiving and
maintaining a head of the subject at least partially immersed in
cool liquid, and a neck support for supporting the neck of the
subject with the head of the subject tilted backwards into the
liquid container. The container can include a liquid reservoir of
cold cooling liquid outside of the receptacle, or the receptacle
itself can serve as the reservoir. The device further includes an
outflow port for delivering cold liquid from the reservoir with one
or more outflow lines (such as catheters) connected to the outflow
port for placement in the aerodigestive tract of the subject. One
or more pumps can withdraw liquid from the reservoir to move it
through the catheter(s) and into the aerodigestive tract. In some
examples, the one or more pumps are capable of delivering 0.1 to 10
L/min of cooling liquid to the aerodigestive tract of the
subject.
[0033] In one embodiment of the device, the liquid reservoir is a
compartment that at least partially abuts the head receptacle, and
a drain communicates between the head receptacle and the liquid
reservoir to return liquid from the head receptacle to the liquid
reservoir. The liquid reservoir may be an at least partially hollow
backboard for supporting a back of a subject, and the backboard
that contains the cooling liquid can be thermally conductive so
that cool liquid within the backboard cools the back of a subject
placed on the board. The backboard may include a top,
body-supporting surface and an inclined neck tilt inducing surface
that inclines into the head receptacle to support the body above
the head receptacle. The top surface of the backboard may incline
upwardly to elevate the thorax relative to the feet, and also
downwardly to provide a downwardly sloping surface on which the
head rests with the neck extended. The top surface of the backboard
may further include a neck support that is placed at the level of
the cervical spine of the subject. The neck support may be
adjustable in height and/or padded.
[0034] One advantage of the disclosed method and device is that it
is suitable for use outside of or in transit to the hospital, for
example in an ambulance or on a stretcher that is being moved. For
example, a wheeled stretcher has a body support surface on which a
back board is placed, a neck support board that inclines from the
back support board into a reservoir for liquid, and a head support
member carried by the neck support board. The position of the head
support member is adjustable along the neck support member to
adjust the head at a desired height (or depth) in the reservoir. In
some embodiments, a wheeled support is provided beneath the
reservoir so that the reservoir can be wheeled in tandem with the
stretcher.
[0035] In some embodiments of the device, the head receptacle
comprises a bottom support surface, a back wall, side walls, and a
front wall, wherein the front wall is shorter than the back and
side walls to support the neck of the subject. The front wall is
adjustable in height to support the neck of the subject at
different heights and may be padded for the protection of the
patient. The head receptacle is surrounded by a container that
serves as the reservoir.
[0036] The system further includes catheters for placement in the
aerodigestive tract of the subject, and a pump for circulating
liquid from the receptacle into the aerodigestive tract.
[0037] In other disclosed embodiments, the brain is cooled by
direct external cooling of the head and cooling of blood that is
delivered to the brain. The head can be placed in a container that
holds a reservoir of circulating cold liquid that externally cools
the brain. Cold liquid can be infused into the upper airway through
catheters placed in the nasal cavity, oral cavity, and/or upper
chest to directly cool the inferior surface of the brain and the
brainstem, and indirectly cool other areas of the brain by cooling
blood that passes through the carotid and vertebral arteries.
Sufficient volumes of cool liquid can be delivered to the upper
airway such that fluid substantially fills the upper airway with
the cool liquid which then flows out of the nose and mouth and into
the reservoir of cool liquid that is circulating around the head in
the container.
[0038] In some disclosed embodiments, the head in the container is
completely submerged in the cool liquid, with the liquid covering
the nose and mouth to help completely fill the upper airway with
the liquid.
[0039] Some devices or systems for carrying out the methods of
cooling the brain include a liquid container for receiving and
maintaining the head of the subject at least partially immersed in
cool liquid, and a source of cool liquid for absorbing heat to
induce brain hypothermia. A plurality of liquid delivery catheters
are connected to the source of cool liquid for insertion into the
aerodigestive tract of the subject for direct delivery of cool
liquid to those sites. A liquid circulation tube is also connected
to the source of cool liquid and is placed in the container to
circulate cooled liquid around the head of the subject in the
container. Pumps are operatively associated with the device to move
liquid from the container through the liquid delivery catheters and
into the patient. The system, for example, cools the outer surface
of the brain through the cranium, cools the inferior surface of the
brain and brainstem through cool liquid delivered into the
nasopharynx, and cools the blood perfusing the brain from the
arteries of the mediastinum and neck (such as the internal carotid,
vertebral arteries, proximal-inferior portions of the cerebral
arteries, proximal portions of the penetrating arteries of the
inferior surface of the brain, etc.) through liquid delivered into
the pharynx and/or esophagus.
[0040] The cool liquid can be maintained, for example, at a
temperature of -30.degree. C. to 20.degree. C. to transfer heat
from the brain at a sufficient quantity and at a sufficient rate to
quickly induce hypothermia. Suitable liquids for this purpose
include, for example, perfluorocarbons, oils, and/or water mixtures
containing salts, simple sugars, organic compounds (such as
propylene glycol), antibacterial agents, mucosal protectants (e.g.,
antioxidants, free-radical scavengers, etc.), and/or electrolyte
additives (e.g., to prevent loss of potassium, calcium, etc., into
the fluid bath, especially when fluid is not recycled to a subject
again).
[0041] The source of cool liquid preferably provides sufficient
liquid to substantially fill the upper airway (including the
nasopharynx, oropharynx, hypopharynx, and proximal trachea) with
the cool liquid. In other embodiments, the source of liquid is also
sufficient to substantially fill the upper esophagus, entire
esophagus, and/or stomach.
[0042] The foregoing and other objects, features, and advantages of
the invention will become more apparent from the following detailed
description, which proceeds with reference to the accompanying
figures.
[0043] Any embodiment of any of the present devices, systems, and
methods can consist of or consist essentially of--rather than
comprise/include/contain/have--any of the described elements and/or
features. Thus, in any of the claims, the term "consisting of" or
"consisting essentially of" can be substituted for any of the
open-ended linking verbs recited above, in order to change the
scope of a given claim from what it would otherwise be using the
open-ended linking verb.
[0044] The feature or features of one embodiment may be applied to
other embodiments, even though not described or illustrated, unless
expressly prohibited by this disclosure or the nature of the
embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
[0045] The following drawings illustrate by way of example and not
limitation. For the sake of brevity and clarity, every feature of a
given structure is not always labeled in every figure in which that
structure appears. Identical reference numbers do not necessarily
indicate an identical structure. Rather, the same reference number
may be used to indicate a similar feature or a feature with similar
functionality, as may non-identical reference numbers. The figures
illustrate the described elements using graphical symbols that will
be understood by those of ordinary skill in the art. The
embodiments of the present devices (and their components), systems,
and methods shown in the figures are drawn to scale for at least
the embodiments shown.
[0046] FIG. 1A is a schematic sectional side view of a human head
and upper thorax depicting one configuration of nasal and oral
catheters inserted to flow cooling liquid through the upper
aerodigestive tract. An embodiment of an endotracheal tube with an
inflated cuff is shown inserted into the proximal trachea. Also
depicted are optional external catheters configured to apply liquid
flow externally against the head.
[0047] FIG. 1B is a schematic sectional side view of a human head
and upper thorax, similar to FIG. 1A, but depicting another
configuration of nasal and oral catheters (e.g., with a catheter
obstructing flow into the esophagus).
[0048] FIG. 2A is a view of the upper thorax and head, illustrating
another configuration of oral and nasal irrigation tubes and
optional external irrigation tubes configured to direct cooling
liquid against the face and head, where the irrigation tubes are
configured to deliver cooling liquid to the esophagus and stomach
for inducing hypothermia in the body (without more selectively
cooling the head and brain).
[0049] FIG. 2B shows the structures of the mediastinum that form a
thermally insulated compartment that helps maintain mediastinal
cooling induced by the methods, systems, and devices disclosed
herein.
[0050] FIG. 3 is a partially schematic side view of the head of a
supine subject placed in a container of cool liquid with liquid
instillation and another configuration of tubes (e.g.,
recirculation tubes inserted in the nose, mouth, and upper
esophagus, and an endotracheal tube in the trachea).
[0051] FIG. 4 is a schematic side view of the head, neck, and chest
of a subject illustrating the upper airway and some of the blood
vessels that can be cooled by circulating cool liquid through the
aerodigestive tract during selective cooling of the brain.
[0052] FIG. 5A is a top view of a head receptacle with a
surrounding cooling liquid reservoir, with a head of a subject
placed in the receptacle. FIG. 5B is a side-view of FIG. 5A
illustrating extension of the neck of the subject. FIG. 5C shows
the device in use, with cooling liquid filling the receptacle. FIG.
5D shows an alternative version of the device with a front wall
having an adjustable height for supporting the neck of a subject in
different degrees of neck extension. FIG. 5E shows the device of
FIG. 5D with the head receptacle at least partially filled with
cooling liquid. FIG. 5F is yet another embodiment of the head
receptacle, in which a mesh net forms the receptacle that supports
the head over the reservoir of cooling liquid, and forms a
permeable barrier through which the liquid returns from the
receptacle to the reservoir.
[0053] FIG. 6A is a side view showing in cross section a back
support and head receptacle, wherein the back support serves as the
reservoir of cooling liquid. FIG. 6B is a view similar to FIG. 6A,
but showing a back support that has an upwardly included surface to
elevate the upper thorax above the waist.
[0054] FIG. 7 is a view of another embodiment of the device in
which a flat body support platform is fixed in, on, or slightly
above a large tub of cooling water with ice floating in it to cool
the water in the tub.
[0055] FIG. 8 is a side view of a patient being transported on a
stretcher, with a head receptacle that also serves as the cooling
liquid reservoir, and the head receptacle moves with the
stretcher.
[0056] FIG. 9A is one example of a block diagram showing the heat
flows impacting the temperature of the brain and body core for a
system that can provide simultaneous brain cooling and body
warming.
[0057] FIG. 9B is another example of a block diagram of heat flows
impacting the temperature of the brain and body core.
[0058] FIG. 10A is an example of a block diagram showing a fluidic
system used to accomplish patient cooling. FIG. 10B is another
example of a block diagram of a cooling system. FIG. 10C is yet
another example of a block diagram of a cooling system.
[0059] FIG. 11 illustrates one configuration of a "long column"
cooling strategy and the resulting fluid flow field. Long column
cooling methods can, for example, permit faster and/or deeper
cooling. As another example, long column cooling methods can allow
for and maintain a larger steady state gradient between brain
temperature and body temperature than other methods. In some
embodiments, the physical length of the column can be lengthened or
shortened depending on a given regime of medications, anesthetics,
and/or agents administered during a procedure, as discussed in
detail below (e.g., the physical length of the column can be
shortened when an intensive anesthetic regime is used).
[0060] FIG. 12 is an example of a block diagram of a control system
used to manipulate patient temperature and irrigation flow rates,
among other things. Dashed lines represent interaction via
information or electrical signals, while solid lines represent
thermal and fluidic interactions.
[0061] FIG. 13 is another example of a block diagram of a patient
temperature control system when an integrated warming device is
used. Dashed lines represent interaction via information or
electrical signals, while solid lines represent thermal and fluidic
interactions.
[0062] FIG. 14 is yet another example of a block diagram of another
patient temperature control system.
[0063] FIG. 15 is an example of a block diagram showing one
embodiment of a cooling system.
[0064] FIG. 16 is an example of a block diagram showing a cooling
unit in thermal communication with a heat exchanger (e.g.,
disposable).
[0065] FIG. 17 is an example of a block diagram showing a simple
feedback control loop designed to control a surface warming device
based on the temperature at the interface between the device and
the skin.
[0066] FIGS. 18A-C are representative sketches of one embodiment of
a multi-function esophageal catheter for use with the described
cooling and temperature management system and exemplary section
views taken along line A-A in FIG. 18A.
[0067] FIGS. 19A-D are representative sketches of one embodiment of
a "double section" balloon esophageal catheter used in certain
embodiments of the described cooling and temperature management
system and exemplary section views taken along line A-A in FIG.
19A.
[0068] FIGS. 20A-C are representative sketches of one embodiment of
a multi-lumen tracheal catheter for use with the described cooling
and temperature management system and exemplary section views taken
along line A-A in FIG. 20A.
[0069] FIGS. 21A-D are representative sketches of one embodiment of
a "double section" balloon tracheal catheter used in certain
embodiments of the described cooling and temperature management
system and exemplary section views taken along line A-A in FIG.
21A.
[0070] FIGS. 22A-B show one example of a flushing concept using a
multi-function tracheal tube and an exemplary section view taken
along line A-A in FIG. 22A.
[0071] FIG. 23A depicts one embodiment of a single use fluid path
system with a recirculating chiller.
[0072] FIG. 23B depicts an electrical schematic of the embodiment
of the system of FIG. 23A.
[0073] FIGS. 23C-D depict various graphical representations of
temperature measurements over time using the system of FIG.
23A.
[0074] FIG. 24A depicts another embodiment of the present systems,
including two recirculating chillers and flow meters.
[0075] FIG. 24B depicts a graphical representations of temperature
measurements over time using the system of FIG. 24A.
[0076] FIGS. 25A-25B depict another other embodiments of the
systems of the present invention with separate fluid return and
fluid supply reservoirs.
DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0077] The following description is exemplary in nature and is not
intended to limit the scope, applicability, or configuration of the
invention in any way. Various changes to the described embodiments
may be made in the function and arrangement of the elements
described herein without departing from the scope of the
invention.
[0078] Although the operations of exemplary embodiments of the
disclosed methods may be described in a particular, sequential
order for convenient presentation, it should be understood that
disclosed embodiments can encompass an order of operations other
than the particular, sequential order disclosed. For example,
operations described sequentially may in some cases be rearranged
or performed concurrently. Further, descriptions and disclosures
provided in association with one particular embodiment or example
are not limited to that embodiment or example, and can be applied,
in whole or in part, to any embodiment or example disclosed
herein.
[0079] As used in this application and in the claims, the terms
"a," "an," and "the" include both the singular and plural forms of
the element(s) they refer to unless the context clearly dictates
otherwise.
[0080] The term "aerodigestive tract" refers to a complex of organs
that, in total, make up the tissues and organs of the upper
respiratory tract and the upper part of the digestive tract. The
aerodigestive tract, as used herein, can include the lips and
mouth, tongue, nose, throat, vocal cords, esophagus, stomach and/or
trachea. The aerodigestive tract does not include the lungs. The
phrase "introducing liquid into the aerodigestive tract" includes
introducing liquids into any part of the aerodigestive tract, such
as the nasal cavity, upper airway (nasal and oral cavity and
pharynx), the nasal cavity and upper airway and esophagus, or the
nasal cavity and upper airway and esophagus and stomach, or any
combination or sub-combination thereof.
[0081] The term "coupled" is defined as connected, although not
necessarily directly, and not necessarily mechanically (e.g.,
electrically, electromagnetically, physically, chemically, etc.).
Two items are "couplable" if they can be coupled to each other.
Unless the context explicitly requires otherwise, items that are
couplable are also decouplable, and vice-versa. One non-limiting
way in which a first structure is couplable to a second structure
is for the first structure to be configured to be coupled to the
second structure.
[0082] The term "substantially" is defined as largely but not
necessarily wholly what is specified (and includes what is
specified; e.g., substantially 90 degrees includes 90 degrees and
substantially parallel includes parallel), as understood by a
person of ordinary skill in the art. In any disclosed embodiment,
the terms "substantially," "approximately," and "about" may be
substituted with "within [a percentage] of" what is specified,
where the percentage includes 0.1, 1, 5, and 10 percent.
[0083] The terms "comprise" (and any form of comprise, such as
"comprises" and "comprising"), "have" (and any form of have, such
as "has" and "having"), "include" (and any form of include, such as
"includes" and "including") and "contain" (and any form of contain,
such as "contains" and "containing") are open-ended linking verbs.
As a result, a device or system that "comprises," "has,"
"includes," or "contains" one or more elements or features
possesses those one or more elements or features, but is not
limited to possessing only those elements or features. Likewise, a
method that "comprises," "has," "includes" or "contains" one or
more steps possesses those one or more steps, but is not limited to
possessing only those one or more steps.
[0084] Terms such as "first" and "second" are used only to
differentiate structures or features, and not to limit the
different structures or features to a particular order or
quantity.
[0085] "Extension" of the neck refers to bending the neck to move
the head posteriorly.
[0086] "Pharynx" refers to the part of the neck and throat situated
immediately posterior to the mouth and nasal cavity, but superior
to the esophagus, larynx, and trachea. It is anatomically divided
into the nasopharynx (posterior to the nasal cavity), oropharynx
(posterior to the oral cavity), and hypopharynx or layngopharynx
(between the oropharynx and the esophagus).
[0087] "Hypothermia" refers to a condition in which body or organ
temperature is below normal physiological temperatures.
"Therapeutic hypothermia" refers to hypothermia induced to attempt
medical benefit in a subject. Inducing "selective hypothermia" does
not require absolute selectivity; relative selectivity of cooling a
target organ or area can occur. Hence inducing "selective
hypothermia" refers to inducing hypothermia in a target organ or
organs to a greater extent or substantially greater extent than in
non-target organs. For example, selective hypothermia may be
induced in the brain or head of a subject by selectively cooling
blood vessels that perfuse that organ as well as selectively
cooling anatomic structures that are contiguous with that organ.
Selective hypothermia need not be absolutely selective, and some
cooling of other organs (or the entire body) can occur. In
particular examples, selective hypothermia can reduce the
temperature of the target organ (such as the brain) by at least
10%, 25%, 50%, or 75% more than the reduction of overall core body
temperature. Inducing "non-selective hypothermia" refers to a
generalized cooling of the body that is not specifically targeted
to any particular organ (such as the brain). However, even with
"non-selective" cooling some preferential cooling of a particular
organ can occur.
[0088] A "non-nebulized" liquid is one that is not turned into a
fine spray or atomized. The non-nebulized liquid therefore emerges
in a continuous liquid stream instead of discontinuous droplets.
The continuous or coherent liquid flow provides greater flow rates
(with consequently greater cooling rates) and can be achieved by
using non-nebulized, but perhaps intermittent introduction of
cooling liquid into the aerodigestive tract.
[0089] "Turbulent flow" of liquid is agitated flow that is not
strictly laminar. Turbulent flow helps disrupt liquid barriers and
increases heat transfer as compared to laminar flow.
[0090] "Forced flow" describes any non-stagnant flow--e.g., moving
liquid driven by a pressure head, pump, or residual kinetic energy.
The flow can be either laminar or turbulent.
[0091] "Upper aerodigestive tract" refers to the portion of the
aerodigestive tract above the esophagus. The "upper airway" refers
to the air passageways above the trachea, which includes the nasal
and oral cavities, as well as the pharynx.
[0092] References to "introducing a catheter" are understood to
refer to introducing one or more catheters. For example,
introducing a catheter into the nasal cavity can refer to
introducing a catheter into each nostril so that there are two
catheters in the nasal cavities. As another example, introducing a
catheter into the nasal cavity can refer to introducing a catheter
into one of the two nostrils so that there is one catheter in the
nasal cavity. Catheters may have multiple lumens to allow passage
of instruments, measuring devices, liquid flows, and/or gas
flows
[0093] "Catheter" refers to a hollow tube configured to be inserted
into a body cavity, duct, or vessel to allow passage of fluid
and/or gases. Catheters may have--but are not required to
have--multiple lumens to allow passage of instruments, measuring
devices, liquid flows and or gas flows. Any use of the term
catheter throughout the application should be interpreted to be
broad enough to include both single- and multi-lumen catheters.
[0094] "Tube" refers to a generally hollow cylinder, especially one
that conveys fluids as a passage. A tube can have--but is not
required to have--multiple lumens, similarly to catheters. A "line"
is a "tube" that can be, but is not necessarily, generally
cylindrical like a "tube."
[0095] "Lumen" refers to an inner open space of a catheter, tube,
or other such member.
[0096] As used herein, a "temperature management kit" refers to a
system that includes a base unit, an interface kit, and any
associated software that can function to control the temperature of
the patient in the manner described herein.
[0097] "User" or "care provider" refers to those taking care of the
patient or those setting up, operating, or otherwise using the
devices, systems, and/or methods disclosed herein.
[0098] A "reusable base unit" refers to a part of a system that is
intended to be used with more than one patient.
[0099] An "interface kit" refers to a part of a system that is
intended to be used only once (e.g., because it comes in contact
with the patient's body or bodily fluids).
[0100] A "control unit" or "control system" refers to a mechanical,
optical, or electronic system used to, for example, maintain a
desired output, receiving and processing measured data from the
patient, comparing it to the user's commands, and adjusting power
and/or flow rates as needed to reach and maintain goal
temperature(s) and/or pressure(s). As an example, a control unit or
control system can be part of a base unit and can include software
responsible for carrying out some or all of the described
procedures.
[0101] The term "reusable cooling system" refers to a component
(e.g., part of the base unit) that causes energy to move to and
from a single use heat exchanger. A reusable cooling system can
include, for example, thermoelectric devices and associated
electronics refrigeration system, and/or other heat pumps or other
means (such as endothermic chemical reaction) for creating a cold
cooling surface.
[0102] A "cooling surface" refers to a part of the cooling system
that is in thermal contact with a single use heat exchanger.
[0103] A liquid flow described as "continuous" or "coherent" is
distinguished from a nebulized flow by having a density of 90% or
more of that typical of the bulk liquid. However, the flow may be
intermittent on timescales greater than about 10 seconds.
[0104] In general, it is believed that the neuroprotective benefits
of temperature management arise from cooling the brain, in
particular, while the observed complications arise from cooling the
body core. Therefore, brain selective devices are in general
preferred over systemic ones. Systemic, non-invasive devices are
sometimes used to cool the entire patient, which eventually leads
to cooling of the brain. However, it is generally recognized that
cooling the body can create complications such as pneumonia,
shivering, low cardiac output, and cardiac arrhythmia that weigh
against the neuroprotective benefits of cooling the brain tissue.
In addition, systemic cooling is typically very slow, as the
thermal mass of the body, intrinsic metabolic heat production, as
well as defense mechanisms (such as vasoconstriction and shivering)
should be addressed. Cooling rates of systemic cooling can often be
slow enough to impair the effectiveness of the therapy.
[0105] Therapeutic devices, systems, and methods are disclosed
herein for cooling the brain, spinal cord, and more generally the
body of a subject to clinically beneficial temperatures that help
preserve tissue function (such as brain function) following
potentially tissue-damaging events, such as hypoxia (as can occur
following cardiac arrest or respiratory failure), neurovascular
events (such as a stroke), direct trauma (such as a closed head
injury or spinal contusion), or perinatal insults (such as
difficult deliveries). However, the treatment can be used for any
person at risk of tissue injury or inflammation damage from a
traumatic or other medical incident. The therapeutic method can be
initiated prior to arrival at a medical center, but it is also
suitable for in-hospital use.
[0106] The therapeutic method may be continued for hours or days as
clinically needed and can be used with other methods of brain or
body cooling. The therapeutic method can also be used as a bridge
to concomitant therapies, such as thrombolysis or thrombectomy (for
treating stroke) and cardiopulmonary bypass (for treating cardiac
arrest). In the event of cardiac arrest, brain cooling may be
initiated before or after spontaneous circulation is reestablished,
and even when spontaneous circulation cannot be reestablished prior
to presentation at a medical center.
[0107] In some embodiments of the new method, the brain is--but is
not required to be--cooled by (either separately or in combination
with) two functional mechanisms: direct head cooling and cooling of
blood that is delivered to the brain. The head can be directly
cooled externally by immersing it completely or partially in a
container through which cold liquid circulates. As another example,
the head can be cooled by applying a well-mixed flow of cold liquid
externally against the head. Direct cooling of the inferior surface
of the brain and brain stem can be achieved by infusing cold liquid
into the upper aerodigestive tract using catheters placed in the
upper airway (for example, into the nasal cavity, nasopharynx, oral
cavity, oropharynx, and/or hypopharynx). By intermittent or
continuous irrigation with non-nebulized cold liquid, an effective
and rapid internal cooling of the nasopharyngeal cavity, upper
airway, or aerodigestive tract occurs.
[0108] Cooling the upper aerodigestive tract and/or scalp causes
blood delivered to the brain to be cooled as it flows through the
arteries of the neck and head. Optional additional cooling is
achieved by delivering cold liquid into the esophagus via a
catheter inserted through the mouth with the tip positioned in (or
near) the esophagus, for example the mid-esophagus. Alternatively,
multiple outlet ports (either from a single or multiple catheters)
can deliver even more cooling liquid in the esophagus. The outlet
ports in the esophageal catheter(s) can deliver the cold liquid
into the proximal, and/or mid, and/or distal esophagus, and/or the
stomach.
[0109] In some embodiments, the cool liquid circulating from the
esophagus and upper airway/aerodigestive tract exits the mouth and
mixes with the liquid surrounding the scalp, whence it is withdrawn
from the container, optionally cooled and optionally returned to
the container, for example through liquid delivery catheters (such
as the catheters in the nose, mouth and esophagus). Cooled liquid
can be cooled and/or stored in a reservoir external to the head
receptacle. In yet other illustrated embodiments described in
greater detail below, the liquid can be cooled in the head
receptacle without withdrawing it from the receptacle (e.g., the
receptacle is the reservoir) by adding ice or other cold items to
the liquid. In yet other embodiments in which cool liquid passively
flows out of the mouth and nose, the cool liquid can be returned to
a cooling reservoir by the action of gravity, for example, by
passing through a liquid permeable net that supports the head, or a
drain in the receptacle that leads to the reservoir.
[0110] While in some embodiments it can be advantageous for the
systems, methods, and devices of the present invention to be used
with an external cooling reservoir, box, and/or receptacle at least
partially surrounding a subject's head, it is not required. In
other embodiments, it can be advantageous to use the systems,
methods, and devices without a reservoir, box, and/or receptacle at
least partially surrounding a subject's head (e.g., to provide
greater access to a subject's head). Similarly, while in some
embodiments, it can be advantageous to permit cooling liquid
circulating within the aerodigestive tract during a procedure to
exit passively from a subject's nose and/or mouth as described
above, it is not required. In other embodiments, and described in
detail below, it can be advantageous to actively remove fluid from
the aerodigestive tract (e.g., using a negative pressure device
(e.g., a suctioning device) coupled to at least one of the present
catheters while the catheter is disposed in a subject's
aerodigestive tract).
[0111] An initial temperature of liquid used for cooling can
comprise various temperature ranges. For example, the initial
temperature of the liquid can be in the range of -30 to 30.degree.
C. (e.g., -30 to 10.degree. C., -20 to 10.degree. C., etc.).
Optimal temperature may vary depending on various factors, such as
body size, procedure type, desired brain/body core temperature
gradient, and the like. For example, a liquid used for cooling can
be maintained at a temperature (such as a substantially fixed
temperature) of less than 30.degree. C., less than 10.degree. C.,
less than -10.degree. C., and the like (such as a temperature of
about -17.degree. C.). The liquid can be maintained at any
substantially constant temperature (for example, within a range of
.+-.2.degree. C.) by equilibration with a heat exchanger at the
desired temperature in a "single fluid pass" configuration or by
circulating it between the receptacle/reservoir and a separate heat
exchanger cooling unit, adding additional cool liquid as required
or by adding cold objects to the reservoir of liquid.
Alternatively, the temperature is maintained by adding ice
(including dry ice) or other cool objects at a desired temperature
to the liquid.
[0112] In embodiments in which the scalp is exposed to cooling
liquid, forced flow of the liquid over the surfaces of the scalp is
achieved, for example, by constantly withdrawing the liquid to be
cooled and reintroducing the cooled liquid under pressure into the
head receptacle (e.g., through a tube directed at the head).
However, other means of liquid agitation within the head receptacle
may also be used. Forced flow over internal and/or external body
surfaces improves heat transfer by reducing the depth of the
boundary layer of immobile cool liquid. Hair may be removed if it
has an insulating effect that interferes with effective rapid heat
exchange.
[0113] One configuration of the cooling method is illustrated in
FIG. 1A, which schematically shows the placement of irrigation
catheters that deliver a flow of cooling liquid to structures that
substantially selectively cool the brain 10 in the head 12 of a
subject 14, as opposed to generalized induction of hypothermia
throughout the body of subject 14. The sectional view shows (moving
anterior to posterior) the nose 16 with nasal cavities 18 (only one
shown) and nasopharynx 20. The bottom wall of nasal cavity 18 is
defined by the palate, which is divided into the anterior hard
palate 22 and posterior soft palate 24. Mouth 26 defines an
entrance to oral cavity 28, which leads to a posterior oropharynx
30. Inferior to oropharynx 30 is hypopharynx 32 that is bounded
anteriorly by epiglottis 34 and leads inferiorly to the anteriorly
situated trachea 36 and posteriorly situated esophagus 38.
[0114] In the embodiments shown, targeted cooling of the brain can
be achieved, for example, by introducing a continuous or coherent
flow of liquid that circulates through the upper airway (e.g.,
above the level of the trachea and esophagus) and includes the
nasal and oral cavities 18 and 28, nasopharynx 20, oropharynx 30,
and hypopharynx 32. FIG. 1A provides an example of how to provide
this continuous flow by introducing nasal catheters 40 into the
nasal cavities and an oral catheter 42 into the oral cavity of
subject 14. First and second nasal catheters 40 (only one is shown
in FIG. 1A) are inserted into each nostril of nose 16 and advanced
until the distal open delivery tip 44 is positioned in the nasal
cavity above the hard palate 22 (although it can alternatively be
positioned above hard palate 22, soft palate 24, or nasopharynx
20). Oral catheter 42 is similarly inserted into the oral cavity 24
with the open delivery tip 46 advanced toward and positioned, for
example, slightly beyond and below soft palate 24 with open
delivery tip 46 positioned in (or near) oropharynx 32. In other
embodiments, however, oral catheter 42 can be positioned before
soft palate 24 (e.g., such that open delivery tip 46 is directed
toward oropharynx 32). To help isolate the lungs from the upper
airway and aerodigestive tract, an endotracheal tube 48 is shown
inserted through mouth 26 and hypopharynx 32 into trachea 36. An
optional inflatable peripheral cuff 50 is shown in its expanded
condition occluding the lumen of trachea 36.
[0115] An inflatable cuff (or balloons)--whether esophageal,
tracheal, or other--can be inflated with gas (e.g., air) and/or
liquid (e.g., water). In some embodiments, the gas and/or liquid
can be chilled to a desired temperature to assist in cooling the
tissue with which the inflatable cuff is in contact (e.g., and by
effect, cooling the blood flowing to the brain). In other
embodiments, the gas and/or liquid can be warmed to a desired
temperature (e.g., with respect to the irrigation fluid) in order,
for example, to improve a contact/interface with surrounding
tissue. Inflating a cuff with fluid can have the additional
advantage of pre-equilibrating the cuff with the cooling fluid in a
subject's upper airway (e.g., preventing and/or eliminating
contraction of the cuff).
[0116] Inflatable cuffs can comprise any biocompatible material
configured to expand in response to a sufficient outward force.
Such material can further be configured such that the cuff responds
to an application of sufficient inward force from a portion of the
aerodigestive tract (e.g., tracheal/esophageal tissue) by
cooperating with the aerodigestive tract to form a substantially
fluid-tight seal (e.g., such that water entering the mouth and/or
nose through catheters is substantially prevented from moving
beyond the cuff). The thickness of the material used to create an
inflatable cuff can be varied depending on a number of factors,
such as, a desired force with which the cuff should expand,
malleability of the cuff in contact with aerodigestive tissue,
desired strength of the cuff, a given procedure, a desired location
of the cuff within the aerodigestive tract, and the like.
[0117] Further, inflatable cuffs can comprise a double balloon
structure having a first opening interior to a first balloon and a
second opening defined by an outer surface of the first balloon and
an inner surface of a second balloon. A first and second opening of
a double balloon structure can be filled with the same or different
substances.
[0118] Inflatable cuffs can also comprise various measurement
devices (discussed in detail below) configured to measure
information about the cuff (e.g., pressure, temperature, volume,
etc.) and/or the tissue (e.g., temperature) with which the cuff is
in contact.
[0119] The illustrated catheters 40, 42, 48 can be single or
multiple lumen catheters. The bores of catheters 40 and 42 are of a
sufficient size to permit a flow of a continuous or coherent column
of cooling liquid through the catheters and out of open tips 44 and
46, respectively, to establish the coherent flow of liquid that
substantially fills the upper airway. One or more optional
fronto-tempero-parietal catheters 52 are schematically shown in
FIG. 1A positioned to direct a forced flow of cooling liquid
against the anterior portion of head 12, for example, against the
fronto-parietal portions of the head (e.g., against the forehead or
side of the head). One or more optional posterior catheters 54 can
also be situated to direct a forced flow of cooling liquid against
a posterior portion of head 12, for example, against the occipital
portion of head 12. Catheters 52 have open tips 56 oriented within
1-5 cm of the surface of the head, and catheters 54 have open tips
58 similarly situation within 1-5 cm of the head surface.
[0120] Although not shown in the schematic illustration of FIG. 1A,
each of the catheters is adapted for operative connection to a
source of liquid for introduction through the catheter. Catheters
40, 42, 52, 54 are adapted for connection to a sufficient supply of
cooling liquid of a temperature adequate to lower the brain to a
targeted temperature (such as 33.degree. C. or less), or by a
targeted change in temperature within a set period of time (such as
5.degree. C. within 30 minutes or less). Endotracheal tube 48 is
adapted for operative connection to a ventilator or other source of
respirable gas that can be introduced under pressure for mechanical
ventilation of the lungs (not shown). Although the illustrated
catheters are shown having end openings for discharging the liquid
from the catheter into the aerodigestive tract, the catheters can
instead be provided with multiple side holes in the distal 5-10 cm
of the catheter to allow liquid to be discharged laterally from the
catheter instead of (or in addition to) discharge from the tip.
Lateral discharge can help promote well-mixed flow within the
aerodigestive tract.
[0121] Cooling liquid is introduced through tips 44, 46, 56, 58 of
tubes 40, 42, 52, 54, respectively, as shown by arrows in FIG. 1A.
The volume of cooling liquid circulates through the upper
airway/aerodigestive tract (e.g., above the level of the esophagus
and trachea), to at least partially fill the upper airway with the
cooling liquid and assure substantial contact between the cooling
liquid and the exposed surfaces of the upper aerodigestive
tract/airway. In some embodiments, the upper airway and upper
aerodigestive tract are substantially filled with the cooling
liquid.
[0122] Many of the surfaces of the upper aerodigestive tract are
irregular (such as the richly vascularized nasal turbinates) and
the flow of liquid that moves along the irregular surfaces of the
airway can provide superior heat exchange to cool the airway. The
mixing induced by a large flow of liquid being introduced into the
confined space of the upper aerodigestive tract and returning
outside of any catheters or tubes through the airway itself further
disrupts any insulative areas as the circulating liquid moves
toward the mouth and nose. In some embodiments, liquid passively
moves out of the mouth and nose as new cooling liquid moves into
the upper airway to continuously replenish the cooling effect of
the liquid.
[0123] FIG. 1B shows another configuration of the systems and
methods illustrated in FIG. 1A. For simplicity, and not by way of
limitation, like parts have been given like reference numbers to
those found in FIG. 1A. In the embodiment shown in FIG. 1B, an
esophageal tube 60 can additionally be inserted through mouth 26
into esophagus 38. Esophageal tube 60 has a distal balloon 62 that
is shown in an inflated condition in the proximal or middle portion
of esophagus 38 to substantially prevent fluid from moving beyond
balloon 62. Additionally, esophageal tube 60 can be operatively
connected to a source of cooling liquid (not shown) to introduce a
flow of liquid through the lumen of esophageal tube 60 and emerges
through side port 64 to thereby serve as an additional source of
cooling liquid circulating through the upper airway.
[0124] The methods of cooling described in FIG. 1A and FIG. 1B are
examples of "selective" cooling of the head and the brain in that
cooling of those structures proceeds faster than cooling of other
parts of the body. However, a certain amount of non-selective
cooling can also occur as well.
[0125] FIG. 2A illustrates an example of a relatively non-selective
cooling method for inducing non-selective hypothermia in a subject
70 by generally cooling the body of the subject without
specifically targeting the brain. FIG. 2A schematically shows the
subject's brain 72, within head 74. One of the two lungs 76 is
illustrated in the chest of subject 70, as is the position of heart
78. The subject's nasal cavity 80 and oral cavity 82 communicate
with esophagus 84 and stomach 86, and trachea 87 that communicates
with lung 76. In the embodiment shown, no tubes are placed in nasal
cavity 80, but an endotracheal tube 88 is positioned in trachea 87
with an optional inflated cuff 90 to isolate the lungs from the
flow of cooling liquid in the upper aerodigestive tract. In other
embodiments, however, tubes can be placed in nasal cavity 80, only,
or in combination with one or more tubes placed in oral cavity 82,
such that the one or more tubes can be disposed in the oral cavity,
the esophagus, and/or trachea (e.g., to achieve a greater cooling
effect). In the embodiment shown, the esophagus and stomach are
cooled by three esophageal tubes, namely an upper esophageal
cooling tube 92 positioned with a single outlet (e.g., an open end)
in the upper esophagus, a middle esophageal cooling tube 94
positioned with a single outlet (e.g., an open end) in the mid
esophagus, and a gastric tube 96 positioned with a single outlet
(e.g., an open end) in the stomach for cooling the stomach.
Although three tubes are illustrated in this example, a single
multi-lumen tube with multiple outlet ports could alternatively be
used. As previously described, side ports instead of end openings
could also be used to increase mixing in the flow.
[0126] Cooling liquid can be introduced through all three tubes and
delivered to different levels of the digestive tract to provide
primary cooling of the esophagus and stomach as the cool liquid
returns from the stomach and esophagus. The cool liquid in the
stomach contacts the rugae that greatly increases the surface area
across which heat exchange with the blood can occur. Cooling liquid
in the esophagus and stomach is also in close anatomic proximity to
the inferior vena cava 98, superior vena cava (not shown),
descending aorta 100, and aortic arch 102 to cool the blood therein
as it moves through body, and particularly as the blood moves
through the structures of the mediastinum.
[0127] Although FIG. 2A only shows tubes inserted in the esophagus
and stomach, it will be understood that cooling of the entire
aerodigestive tract can occur by side ports or by retroflow of cool
liquid through the aerodigestive tract to the mouth and nose. In
addition, irrigation catheters can be inserted in the mouth and
nose as in FIG. 1A to further increase the flow of cooling liquid
through the aerodigestive tract.
[0128] External liquid application tubes 104 and 106 can optionally
be positioned to apply a forced flow of liquid externally to the
head of the subject. Tube 104 is positioned to flow liquid against
the frontal area of the head (for example, against the forehead)
and tube 106 is positioned to flow liquid against the occipital
region.
[0129] FIG. 2B illustrates that the mediastinum is an anatomic
compartment that is somewhat insulated and therefore can retain the
cooling effect of the liquid introduced through the esophageal
tubes. The mediastium contains the heart, the great vessels of the
heart, esophagus, and trachea, and is insulated laterally by the
air-filled lungs and inferiorly by the stomach.
[0130] All of the cardiac output passes through the veins of the
mediastinum. Internal cooling of the mediastinum can be
accomplished by cooling substantially all of the aerodigestive
tract, from the nares to the pyloris (excluding lungs). The
mediastinum is insulated from heat from the rest of the body by the
lungs, larynx, and stomach. The lateral aspects of the mediastinum
are bordered by the lungs, which have low mass and are kept cool by
the normal function of ventilation. The inferior aspect of the
mediastinum can be cooled by cooling the stomach. The superior
aspect of the mediastinum, e.g., the neck, can be cooled by cooling
the upper airway. Insulation of the mediastinum enables cooling of
the venous blood in the vena cava more efficiently than if similar
cooling were to be performed on the vena cava within the abdomen.
If vena cava cooling were attempted in the abdomen, heat from the
surrounding organs would also be delivered to the vena cava, which
could significantly impede cooling.
[0131] FIG. 3 provides an example of another brain cooling device
110 for carrying out the selective cooling method, wherein a
container 112 at least partially encloses a head 114 of a subject
116 who is in a supine position (with the face up). Head 114 can be
partially or totally immersed in cool liquid 118, but the
illustrated embodiment shows total immersion of the head and face.
In the embodiment shown, the container 112 is a rectangular or
square box having a solid flat bottom wall 120, three solid upright
side walls 122 (only one is shown in FIG. 1), and open top face
124. Side walls 122 are connected to bottom wall 120 with liquid
tight seals. Each of side walls 122 is also connected to adjacent
side walls 122 with liquid tight seals. One of side walls 122
(e.g., side wall 126) can be configured to receive a subject's head
and/or neck. The bottom wall 120 and side walls 122 and 126 may,
for example, be preformed out of contiguous material, as in a
seamless unitary piece of molded plastic. Open top face 124 defines
a square or rectangular opening large enough to provide access to
the entire face. An upright side wall 126 defines a head and/or
neck receiving opening that contains an annular flexible seal 128
to inhibit flow of liquid from container 112 (e.g., and sized to
adjustably accommodate a subject's neck). An overflow trough 130
may extend along the bottom edge of face 126 to collect liquid that
leaks through the seal such that the liquid can, for example, be
re-circulated to the container by a recirculation pump
(recirculation tubing not shown). For example, the dimensions of
the container can be approximately 25 to 50 cm in length, width,
and height for an adult-sized box and 10 to 25 cm on all sides for
an infant-sized box.
[0132] The reservoir of cool liquid 118 can substantially fill
container 112. The liquid in the box has a top liquid level 132
that, in the illustrated embodiment, is within 2-10 cm of the top
edge of the box, such that the liquid completely submerges head 114
below liquid level 132. With the liquid at this level, both the
nose 134 and mouth 136 of subject 116 are completely covered with
liquid, and the upper airways can passively fill with liquid from
the container in addition to being actively filled with liquid
pumped into the airway, as described below. The area around the
head and in the upper airways can therefore be a substantially
uninterrupted continuum of cooling liquid that can establish
thermal exchange with the anatomic structures that come into
contact with the continuum of liquid. In other embodiments, as
described above, top liquid level 132 can comprise a level such
that mouth 136 and/or the nose 134 are not completely submerged in
cool liquid 118. In such embodiments, head 114 can still be cooled
passively by cool liquid 118, and the upper airways can be actively
filled with liquid pumped into the airway, as described below.
[0133] In the embodiment shown in FIG. 3, device 110 can be
configured to control the temperature of the liquid in container
112. Device 110 can be configured in various ways to permit control
of the temperature of the liquid in the container, such as, for
example, configuring container 112 similarly to a refrigeration
unit, adding cool objects (such as ice) to the liquid, and/or using
endothermic chemical reactions (such as ammonium nitrate in water)
in the walls of the container to cool them. In the embodiment
shown, liquid in container 112 is cooled externally to the
container by pumping it from the container to a heat exchanger 144,
where it is cooled and pumped back to the container. The heat
exchanger can be of any type, such as a shell and tube heat
exchanger, a plate heat exchanger, a regenerative heat exchanger,
an adiabatic wheel heat exchanger, a fluid heat exchanger, or a
dynamic scraped surface heat exchanger. Additional information
about such devices is readily available, for example, in Sadik
Kakaq and Hongtan Liu Heat Exchangers: Selection, Rating and
Thermal Design, 2nd Edition, CRC Press (2002) (ISBN
0849309026).
[0134] FIG. 3 further shows an intake conduit 140 that extends from
container 112 to a liquid pump 142. Pump 142 is coupled to heat
exchanger 144. Outlet conduit 146 extends from heat exchanger 144
and communicates with an elongated distribution conduit 148 that
provides multiple catheter connection outlets. Although the
illustrated embodiment shows a single pump, more than one pump can
be used. The pump can also be manually operated (for example, by
manually rotating or reciprocating a pump handle) or non-manually
operated (for example, by actuating an electrically operated
pump).
[0135] Liquid circulation conduits of various lengths are connected
to the outlets on distribution conduit 148 and extend through the
open top face 124 of container 112. Four of them are liquid
circulation tubes 150, 152, 154, 156, which can deliver flow of
liquid to the scalp and face. Tubes 150 and 156 extend
substantially to the bottom of container 112 for deep recirculation
of liquid. Tubes 152 and 154 extend into the top portion of
container 112 to provide more recirculation of liquid in the
container. Another of the liquid circulation conduits is a first
liquid delivery catheter 158 for delivering cool liquid to the
nasal cavity 160 of the subject. First liquid delivery catheter 158
can be any length sufficient to extend from distribution conduit
148 to a distance of about 3 to 6 cm into the nasal cavity 160 with
the outlet of catheter 158 directed at (or near to) nasopharynx
161. Another of the conduits is a second liquid delivery catheter
162 for delivering cool liquid to the oral cavity 164 of the
subject. Catheter 162 can be any length sufficient to extend a
distance of about 6-12 cm into oral cavity 164 with the outlet of
catheter 162 directed at (or near to) oropharynx 168.
[0136] In the embodiment shown, device 110 further comprises a
third liquid delivery catheter 166 configured similarly to a
nasogastric tube. Catheter 166 extends from distribution conduit
148 and can comprise any length sufficient to extend through oral
cavity 164, oropharynx 168, hypopharynx 170, and into esophagus 172
(e.g., 25 to 30 cm beyond mouth 136). Catheter 166 can be a
multi-lumen catheter with a balloon tip 174 that is selectively
inflatable, for example, by using a source of pressurized air
(e.g., a syringe (not shown)) that introduces the air through one
of the lumens to the balloon tip 174. Another lumen of catheter 166
opens to a side port 176 that is in fluid communication with
distribution conduit 148 (e.g., such that side port 176 can deliver
cool liquid into the proximal esophagus). Side port 176 is proximal
to balloon tip 174 so that when balloon tip 174 is inflated the
liquid delivered into esophagus 172 does not flow beyond balloon
tip 174 into the distal gastrointestinal tract (such as the
stomach), but can instead move in a proximal direction through the
upper airways.
[0137] Device 110 can also comprise multi-lumen endotracheal tube
180 having a conventional coupling collar 182 configured to be
coupled to a source of ventilation (not shown). Suitable sources of
ventilation include any device configured to introduce a non-toxic
fluid (such as a gas) with oxygen in it. Examples of such sources
include a manual ventilation bag or a mechanical ventilator that
communicates with the primary lumen of tube 180. The primary lumen
of tube 180 is in fluid communication with the lower airways and
lungs. Endotracheal tube 180 includes a conventional distal cuff
184 that can be selectively inflated (e.g., after insertion) by
introducing a fluid (e.g., a pressurized fluid, such as gas from a
syringe) through a secondary lumen of tube 180 to secure the tube
in place within the trachea 186, to provide an effective seal
between tube 180 and the walls of the trachea (e.g., improving
efficiency of ventilation), and to substantially prevent the entry
of liquid from the upper airway into the lower airways and
lungs.
[0138] Although the illustrated embodiment of endotracheal tube 180
in FIG. 3 includes cuff 184, the cuff is not always required to
substantially seal the airway. For example, in small or pediatric
subjects, the endotracheal tube itself may be large enough to
effectively occlude passage of liquid between tube 180 and the
walls of trachea 186. In still other embodiments, endotracheal tube
180 can be configured to prevent a patient's tongue from
interfering with the cooling procedure. In the illustrated
embodiment (FIG. 3), a suction port 188 is located on the side of
tube 180 proximal to cuff 184. Port 188 communicates with a
tertiary lumen in tube 180 and is coupled (e.g., connected) to a
source of negative pressure source (not shown) that is configured
to withdraw liquid from the trachea. The removed liquid can be
recirculated into the reservoir of liquid 118 in container 112.
[0139] In use, head 114 of subject 116 in need of brain cooling is
placed in container 112 by inserting head 114 through flexible seal
128. A thickened liquid-resistant emulsion or gel (such as
petroleum jelly) can be applied externally in a continuous ring
around the neck to enhance the liquid-resistant seal. A soft,
liquid-resistant foam strip can also be placed around the neck and
may be layered to achieve a desired thickness. Flexible seal 128
can be configured to provide a substantially liquid-tight seal
without obstructing arterial or venous flow of blood through the
neck. In some embodiments, a plastic liner (not shown) can also be
placed in container 112 around head 114 to provide an additional
barrier to loss of liquid from container 112.
[0140] The subject 116 may optionally be prepared for the brain
cooling procedure by removing hair from the head, for example, by
cutting the hair or shaving the head to improve conductive loss of
heat externally from head 114 to surrounding cool liquid 118. If
the subject is conscious, sedation may also be administered (for
example, intravenously administering a benzodiazepine or narcotic)
to lower the level of consciousness and/or induce transient
amnesia. Once the subject's head 114 is positioned within container
112, open top face 124 of container 112 provides access to the
interior of the container. Deep circulation tubes 150 and 156 can
be positioned around head 114 with their outlets proximal to bottom
wall 120. Superficial circulation tubes 152 and 154 can be
positioned above head 114 with the outlets of tubes 152 and 154
directed at the subject 116 (e.g., at the face and scalp). Catheter
158 can be lubricated in a conventional fashion and can be inserted
through a nostril into nasal cavity 160 (e.g., 3 to 6 cm, or such
that the tip of catheter 158 is adjacent to (or near) the
vascularized surfaces of the turbinate mucosa and near the
cribiform plate of the ethmoid bone that supports the inferior
surface of the cerebral cortex) with the outlet of catheter 158
directed at (or near) nasopharynx 161. Esophageal catheter 166 is
inserted through the mouth (e.g., 25 to 30 cm) into the proximal
esophagus 172. Cuff 174 can be inflated after esophageal catheter
166 is positioned appropriately. Further, endotracheal tube 180 can
be inserted into trachea 186, and cuff 184 can be inflated. The
tertiary lumen of endotracheal tube 180 is connected to a negative
pressure source (e.g., a suction device) such that fluid can be
removed from trachea 186.
[0141] Liquid pre-cooled to a desired temperature is introduced
into container 112 until the liquid level 132 reaches a desired
level (e.g., above the intake level of intake conduit 140). Liquid
can be circulated by activating pump 142. Pump 142 is configured to
remove liquid from container 112 through conduit 140 and into heat
exchanger 144. Pump 142 can pass liquid to heat exchanger 144 under
pressure (e.g., 20-60 cm H.sub.2O). Liquid can then exit heat
exchanger 144 through outlet conduit 146 and into distribution
conduit 148. The liquid is then distributed among the outlets and
respective conduits that lead to container 112. Forced flow can be
induced in container 112 around the head by introduction of cool
liquid through circulation tubes 150, 152, 154, and 156. This flow
can enhance heat transfer from the surface of the head and/or
face.
[0142] Pump 142 also circulates the cool liquid through tube 158
into the nasal cavity, through tube 162 into the oral cavity, and
through tube 166 and out of port 176 into the proximal esophagus.
The liquid introduced through the tubes merges with cool liquid
that passively enters from container 112 to substantially fill the
upper airways with a cool liquid that is in a substantially
uninterrupted liquid continuum with the reservoir of cool liquid
around head 114. A continuous recirculation of liquid occurs from
the upper airways to the reservoir of liquid around the head and
back into the upper airway. The liquid may also be continuously
cooled to maintain a desired temperature that induces rapid cooling
of the brain to a desired therapeutic temperature.
[0143] As previously noted, the neck of the subject rests in an
opening in one wall of the container. The opening is provided with
a sealing means, such as a circumferential flexible sealing
material that circumscribes the neck to help enhance the
liquid-tight seal. The liquid-tight seal around the neck can
include a thickened liquid-resistant emulsion or gel (such as
petroleum jelly) that is applied to the skin to make a continuous
ring around the neck. A soft liquid-resistant foam strip may be
placed around the entire circumference of the neck (for example,
over the gel) and may be layered to achieve a desired thickness.
Finally, the flexible sealing material can be tightened around the
neck to a pressure sufficient to provide a substantially
liquid-tight seal without obstructing arterial or venous blood flow
in the neck.
[0144] In one embodiment, the neck-receiving opening is a
"U"-shaped opening in the side wall 126 of container 112, and the
width of the "U" is wider than the neck. Attached to the inner
edges of the opening is a liquid-resistant flexible material (such
as rubber or vinyl). At least 2 inches of free material extends
from the inferior aspect of the defect and sufficient material
extends from each lateral aspect of the defect to substantially
extend to the other side of the opening. To finish the seal around
the neck, the excess material superior to the anterior surface of
the neck can be held together by a fastening device (e.g., clips).
The excess material from both sides (if any) can be wrapped around
each other before being temporarily fastened (e.g., clipped)
together.
[0145] FIG. 4 shows a shaded area that corresponds to the upper
airway that can be filled with cool liquid as discussed in the
present invention. The upper airway includes the nasal cavity,
nasopharynx, oral cavity, oropharynx, and hypopharynx. The upper
airway is defined by the walls of the pharynx that are laterally
flanked in close association on either side by major blood vessels
that perfuse the brain. As shown in FIG. 4, these blood vessels
include common carotid artery 202 and internal carotid artery 204,
which in turn supplies anterior cerebral artery (not shown) and
middle cerebral artery 206. Another blood vessel in close anatomic
association to the upper airway includes the vertebral artery 208,
which is a branch of the subclavian artery and that in turn forms
the basilar artery 210 that supplies blood to the vertebrobasilar
system. The blood flowing through the arteries of the neck can be
conductively cooled by close association with a cool liquid that
fills the upper airway, and this cooled blood can quickly lower the
temperature of the brain as the blood perfuses the brain.
[0146] Further cooling of the blood that perfuses the brain can be
achieved by the introduction of cool liquid into the proximal
esophagus where the cool liquid comes into closer contact with
mediastinal and lower neck structures, including the common carotid
artery 202.
[0147] In this novel therapy, cooling of the blood can start in the
aortic arch if there is cold liquid flow in the esophagus and can
continue throughout the length of the common and internal carotid
arteries, which are in close proximity to the upper airway filled
with circulating cold liquid. The posterior circulation (vertebral
and basilar arteries) can also be cooled. Cooling can continue in
the Circle of Willis, itself, which is separated from the upper
airway by a thin layer of soft tissue and bone. In many cases,
total carotid blood flow is approximately 0.8 L/minute. This blood
is cooled by delivering sufficient cold liquid to fill the
esophagus and upper airway to achieve a sufficiently large and/or
rapid drop in peri-arterial tissue temperature. Blood moves very
rapidly from the heart to the brain and does not spend significant
time in in contact with surrounding tissue. Nasal-based selective
cooling strategies do not provide sufficient time for the blood to
equilibrate with surround cool tissue as it passes from the heart
to the brain. Irrigating the nose, pharynx, and esophagus creates a
long cooling column of cold tissue with which the blood can
equilibrate, leading to greater degrees of equilibration and
cooling for the arterial blood. Direct cooling of the scalp and
upper airway can complement hematogenous cooling, as it also
results in a temperature gradient within the brain, with surface
temperatures colder than deep in the brain. This gradient is offset
by flowing blood since the cerebral arteries traverse long
distances along the relatively cooler surface of the brain before
delivering cooled blood to deeper brain structures.
[0148] Using the disclosed method, focal or isolated cooling of the
head and/or brain is achieved without the adverse physiological and
medical consequences or technical difficulties of cooling the
entire body or large portions of it. Brain cooling can be applied
continuously or intermittently for a sufficient period of time to
avoid damage to the brain, and this period can extend for minutes,
hours, days, or weeks. In some embodiments, the cooling continues
for at least 3 hours, at least 4 hours, at least, 8 hours, at least
12 hours, at least 24 hours, at least 48 hours, at least one week,
or longer. The period of time during which cooling is continued is
determined by the condition of the patient and the clinical
judgment of medical personnel. The temperature of the cool liquid
can be changed over time in accordance with therapeutic needs. For
example, the liquid may initially be cooled to 10.degree. C. or
less (for example, less than zero .degree. C.) to induce rapid
brain cooling and inhibit the development of brain edema, adverse
metabolic changes, or reperfusion injury. After the first few hours
or even days of use, the temperature of the liquid can be
increased, for example to 20-30.degree. C., to cool the brain with
a lesser risk of hypothermic damage to soft tissues.
[0149] This method can produce cerebral cooling, for example, in an
estimated 5-15 minutes compared to 3-5 hours demonstrated in human
studies with many other prior art hypothermic treatments. Therapy
may be started in the field (outside a hospital setting) to
accelerate the initiation of treatment and reduce the elapsed time
to achieving the temperature goal following the onset of illness.
The devices, systems, and methods can be used by someone having
only basic emergency medical skills, such as the ability to place
the catheters and insert an endotracheal tube. The simplicity of
the method will also allow for rapid application of treatment in a
broad array of clinical situations. The cool liquid can be--but is
not required to be--significantly cooler than ice water used in
previous human studies and most animal studies, thereby providing a
large temperature gradient that promotes deeper and more rapid
brain cooling.
[0150] Combining the scalp, upper airway, and cerebral blood
cooling provides rapid and effective cerebral cooling. The method
is particularly effective because it can optionally cool all of
these structures using a common pool of circulating cold liquid.
This method of aggressive local cooling is believed to be effective
at rapidly cooling the brain even in the absence of spontaneous
circulation, although circulating blood is believed to further
accelerate the cooling. The disclosed method also permits deeper
levels of hypothermia to be achieved, which may help to realize the
possible benefits of "suspended animation." This treatment also
leaves open the possibility of salvaging life and neurological
function even in those who do not achieve restoration of
spontaneous circulation in the field. After arrival at an
appropriately equipped medical center, whole body and brain blood
flow can be reinstituted using cardiopulmonary bypass while more
aggressive and time consuming attempts to restore and maintain
spontaneous circulation are explored. If the brain is cooled,
greater neurological recovery can be achieved even if the
restoration of circulation is significantly delayed.
[0151] The circulation of cool liquid around the head can also be
effective, though it is not required. Factors that functionally
insulate the scalp from local hypothermia treatment include scalp
hair, the boundary layer effect, and layers of material and air
between a cold helmet and the scalp. The direct contact of scalp
structures with the circulating liquid helps avoid these
problems.
[0152] Direct cooling of the inferior surface of the brain is
believed to occur more rapidly than scalp cooling due to thinner
protective layers of bone and soft tissue. Bone between the upper
airway and the brain is approximately half as thick as bone in the
scalp and the soft tissue layer is 1/4 the thickness of the
scalp.
[0153] An additional example of a device suitable for use with
either selective or non-selective cooling is shown in FIGS. 5A-5C.
The device is a head cooling box 220 having a rectangular base 222,
a rectangular rear wall 224, two opposing side walls 226, and a
front wall 228. Each of walls 224 and 226 are sufficiently high to
extend above the head 230 of a subject within the box, even when
the head is tilted with the head in extension as in FIGS. 5A-5C.
However, front wall 228 has a cut-out support portion 232 (FIG. 5A)
for receiving the neck of the subject.
[0154] Spaced from and parallel to the outer walls of box 220 are a
set of inner walls that form a head receptacle 234 that is
sufficiently large to receive the head 230 as shown in FIGS. 5A-5C,
with the neck of the subject resting on support portion 232.
Between the head receptacle and the outer walls the box forms a
reservoir 238 that partially or completely surrounds receptacle 234
for storing a sufficient volume of cool liquid to circulate through
the subject and to be applied externally against the scalp.
Reservoir 238 extends behind and below receptacle 234 and
communicates with receptacle 234 via one or more openings that form
drains 240, 242, and 244. In the illustrated embodiment, drain 240
is in a rear wall, drain 242 in a bottom wall, and drain 244 in a
front wall of receptacle 234. An upper port 246 extends through
rear wall 224 near the top of box 220, and a lower port 248 extends
through rear wall 224 near base 222 of box 220.
[0155] In use, the head 230 of a subject in need of treatment can
be placed in box 220 with the neck in cut-out portion 232 and the
head tilted back in extension. Cool liquid is introduced into
reservoir 238 to provide a large volume of cool liquid that can
then be circulated though irrigation catheters (not shown) into the
aerodigestive tract of the subject as described earlier. The cool
liquid is initially delivered into reservoir 238 through upper port
246 and is subsequently withdrawn through lower port 248 and
returned through drains 240 and/or 242 and/or 244 after coming into
contact with the subject. As liquid is introduced into the
aerodigestive tract, it flows into and through the aerodigestive
tract until it eventually passively exits the mouth and nose of the
subject without being suctioned or removed through a catheter or
other tubing. As the liquid emerges from the mouth and nose, it
collects in receptacle 234 around head 230 to further cool the head
externally to lower brain temperature and drains into reservoir 238
via drains 240-244. The rate at which liquid can return from
receptacle 234 to reservoir 238 through one of more of the drains
is adjusted by the degree to which the drains are opened, and the
position and number of open drains. In the illustrated embodiment
of FIG. 5C, bottom drain 242 is open while side drains 240 and 244
are closed so that liquid in receptacle 234 passively flows under
the influence of gravity into the underlying portion of the
reservoir, as shown by the arrow 250. Adjusting the rate at which
liquid drains from receptacle 234, relative to the rate at which
liquid enters the receptacle, determines the level of liquid in
receptacle 234.
[0156] In the illustrated embodiment of FIG. 5C, the liquid level
in surrounding reservoir 230 is lower than the level of bottom
drain 240, which permits drainage through bottom drain 242.
However, in those instances in which a larger volume of cool liquid
is provided in surrounding reservoir 238, the liquid is still
maintained at a level below side drains 240 and 244 which are open
(while bottom drain 242 is closed).
[0157] An alternative embodiment is shown in FIGS. 5D and 5E, in
which corresponding parts from FIGS. 5A-5C are given like reference
numbers for simplicity, but not by way of limitation. This
embodiment differs from the prior version, however, in that the
front wall 228 has a height adjustment member 252 that fits on
front wall 228 and can be moved toward and away from base 222 to
adjust the height of the support for the neck of a subject.
Adjustment member 252 is capped with a cushion 254 for protection
of the neck of the subject and allows for a variable amount of neck
extension. The top of reservoir 238 is also covered by a lid 256
that pivots at hinge 258 to open and close reservoir 238. The
reservoir may be opened, for example, to add ice or other cold
objects to reservoir 238 when cooling of liquid within it is
desired.
[0158] Yet another embodiment of the box is illustrated in FIG. 5F
wherein the box 220 forms the reservoir for holding cold liquid,
and the front wall of the box is of a reduced height or has a
cut-out portion for receiving the head with the neck supported on
cushion 254 of height adjustment member 252. However, the head
receptacle is formed by a liquid permeable net 260 that covers
receptacle 238 for holding the head of the subject during
hypothermic treatment. Net 260 is secured along one edge to front
wall 228 below the level of padding 254 and along an opposite edge
to rear wall 224 at the top of box 220. Net 260 therefore forms a
liquid permeable support sling for the head of a subject, so that
as liquid flows through then out of the aerodigestive tract, the
liquid spills on to and through net 260 to be returned to
underlying reservoir 238.
[0159] In the embodiment of FIG. 6A, the cooling device is in the
form of a backboard 270 that contains both a head receptacle 272
and a reservoir 274 for holding a supply of cool liquid. Receptacle
272 and reservoir 274 are in a side-by-side relationship with one
another instead of the reservoir surrounding the receptacle as in
previously described embodiments. Backboard 270 has a flat
rectangular base 276 that is large enough to accommodate the upper
portion of a body, for example, from the waist or mid-thorax to the
top of the head. A top surface of backboard 270 is formed by a flat
body support 278 that is spaced from and held parallel to base 276
by opposing sidewalls 271 (only one of which is shown in phantom),
an upright bottom wall 280, and an inclined top wall 282 that
separates reservoir 274 from receptacle 272. Sidewalls 271 are of
the same height as the top of receptacle 272 to thereby also form
the sidewalls of receptacle 272.
[0160] Inclined wall 282 slopes from body support surface 278 down
to bottom surface 280 of receptacle 272. A drain 284 is provided
through inclined wall 282 near the junction of wall 282 with
support surface 278 to drain liquid from receptacle 272 back into
reservoir 274 when the level of liquid in receptacle 272 rises
above the level of liquid in reservoir 274, as illustrated by the
arrow through drain 284 in FIG. 6A. A cushioned neck support 286 is
positioned on body support 278 near inclined wall 282 to protect
and assist with the extension of the neck of a subject placed on
backboard 270.
[0161] In use, a subject can be placed face-up on backboard 270
with the neck extended and the head in receptacle 272. The desired
irrigation catheters are inserted in the aerodigestive tract of the
subject (not shown) and liquid from reservoir 274 is pumped through
the catheters into the aerodigestive tract for cooling the patient.
The irrigation liquid then flows out of the nose and mouth of the
subject and collects in reservoir 272 to be returned to reservoir
274 though drain 284. Backboard support 278 is preferably thermally
conductive (for example made of metal) so that the cool liquid in
the backboard also cools the body of the subject directly. This
direct cooling of the subject's back is particularly advantageous
for providing cooling of the spine in patients who may have
incurred a spinal cord injury that could benefit from such cooling
to reduce inflammation and swelling.
[0162] Another embodiment of the backboard cooling device is shown
in FIG. 6B, which is similar to the embodiment of FIG. 6A, except
that body support surface 278' is inclined upwardly to lift the
shoulders and neck of the subject. Raising the upper torso in this
fashion helps protect the airway and inhibit the entry of liquid
into it. It also appropriately positions the head of the patient
for intubation and introduction of the irrigation catheters in the
aerodigestive tract. The backboard cooling device of FIG. 6B is
also shown placed under the back of a patient who is lying face up
on a stretcher 288, so that the cooling method can be performed on
the subject either in a hospital on en route (for example, while in
an ambulance or in transit to a hospital).
[0163] The embodiment of FIG. 7 illustrates an embodiment of the
cooling device that is suitable for treating a subject who has
sustained potential spine injuries and requires stabilization of
the spine to avoid additional injury, such as damage to the spinal
cord. This embodiment includes a large rectangular tub 290 that is
longer and wider than a flat body support board 292 that is
suspended above or within tub 290. Support board 292 has lateral
extensions that form right and left arm support members 294 and 296
and a superior extension that forms a head support 298. In some
embodiments, tub 290 is filled with liquid 300 that contains
sufficient ice 302 to cool liquid 300 to a desired temperature. In
other embodiments, tub 290 can be filled with cooled fluid from a
chilling unit and continually refreshed with cooled recirculated
liquid. Tub 290 therefore provides an underlying large reservoir of
cool liquid for introduction through irrigation tubes (not shown)
into the aerodigestive tract of a subject placed on support board
292. In some embodiments, a patient (not shown) can be positioned
supine on support board 292 with the head turned to the side so
that internally circulated liquid (and/or any liquid sprayed on the
head) can return passively to tube 290 to be cooled there for
recirculation to the patient. In other embodiments, as discussed in
detail below, liquid can be actively removed (e.g., suctioned
through at least one catheter) from the patient.
[0164] FIG. 8 illustrates a mobile version of the cooling device in
which a subject 302 is lying supine on a stretcher 304 that is
supported by wheels 306 for transportation of the subject on the
stretcher. A separate reservoir 308 is supported on a cart 310
having an adjustable height, and which is also supported on wheels
312 for movement with the stretcher. Reservoir 308 is a large
capacity tank that has a cut-out or reduced height portion 311 in
which the neck 314 is placed so that the head 316 of the patient
can be tilted back and into reservoir 308. A backboard is placed
under the back of the patient to support the back and head. The
backboard is an angled member that includes several sections: a
flat back support 318 for horizontal placement on stretcher 304, an
inclined neck support 320 that fits into reservoir 308 through the
neck-receiving portion of the reservoir, and a flat head support
322 that is secured to neck support 320 and held substantially
parallel to back support 318. Head support 322 mates with a series
of ratchets or support grooves 324 on neck support 320 so that the
position of head support 322 can be adjusted along neck support 320
while maintaining the substantially parallel relationship between
head support 322 and back support 318.
[0165] In use, the subject 302 can be placed supine on stretcher
304 with back support 318 under the back of the subject, the neck
positioned in cut-out portion 311, and head 316 tilted back over
the top edge of stretcher 304 with head 316 in reservoir 308, which
also serves as the receptacle for holding the head. The position of
head support 322 is adjusted to support the crown of head 316 at a
desired depth within reservoir 308. Reservoir 308 contains cool
liquid 326 up to a level that covers the crown of head 316 to
provide external cooling of the head (or below the head if scalp
cooling is not desired). As described in connection with other
embodiments, irrigation catheters (not shown) are inserted in the
subject 302 and cooling liquid 326 is pumped from reservoir 308
into the aerodigestive tract of the subject to achieve the desired
rate and degree of cooling. Since both the reservoir and stretcher
are on wheels, they are transported in tandem to administer the
hypothermia therapy to the subject during transport.
[0166] Additional details about the disclosed methods, systems, and
device are provided in the following sections.
[0167] Temperature of the Liquid
[0168] Since permanent brain injury is a major cause of death and
disability, more effective methods of brain cooling will benefit a
subject's overall medical recovery even if these treatments risk
transient damage to other tissue beds. While frost-bite can
sometimes occur at temperatures less than 0.degree. C.,
perfluorocarbon (PFC) and other liquids at temperatures used herein
are believed to be more beneficial than harmful in this method. For
example, household freezers maintain their contents at -17.degree.
C. and food (such as ice cream) is consumed at this temperature
without damage to the mouth or esophagus. Likewise, cold items from
a freezer can be placed on damaged skin to reduce swelling (ice
packs to traumatized areas) without unacceptable risk of tissue
necrosis.
[0169] The esophagus and upper airway are resilient to a variety of
damaging stimuli, such as acid reflux, toxic injections, radiation,
and chemotherapy. The lungs, upper airways, and skin have been
exposed to 0-4.degree. C. water/saline in cold water drowning
without significant sequela. A lung has been infused with
sufficiently large volumes of 4.degree. C. PFC without significant
adverse effects, so cold biocompatible liquids that may
inadvertently enter the lungs is unlikely to be harmful.
[0170] Beneficial results of brain cooling can be seen, for
example, with cerebral cooling to approximately 33.degree. C.
However, the brain can tolerate much lower temperatures. Animals
have had their brains cooled to 10-26.degree. C. and subsequently
recovered without significant neurological damage. Humans have been
found at 26.degree. C. and subsequently recovered without
significant neurological damage. Based on this information, it is
believed that the disclosed hypothermic treatment can be used with
an acceptable therapeutic risk if the cooled liquid is at any
temperature below about 30 or 32.degree. C., and above -20.degree.
C., for example, above -10.degree. C., zero .degree. C., 10.degree.
C., or 20.degree. C. Brief skin and upper airway exposures to
liquid with temperature between -30 to -20.degree. C. may also
carry an acceptable risk of soft tissue injury. Therapeutic risks
of cold damage to soft tissue can also be reduced by inducing the
hypothermic cooling at a lower temperature and then gradually
increasing the temperature as the risk of soft tissue damage
increases and the risk of permanent brain damage decreases.
[0171] Precooling the Brain
[0172] The disclosed brain cooling method has been described in
connection with the treatment of cardiac arrest, stroke, brain
injury, and other conditions. However, the method can also be used
prophylactically, for example, to prepare a patient for
cardiovascular surgery in which the patient is placed on a
heart-lung bypass machine. Prior studies have shown good outcomes
of cardiac surgery performed on humans externally cooled to
25.degree. C. with ice baths. Such patients have had encouraging
outcomes after circulatory arrest that lasted for 30 to 77 minutes
that was not supported by heart-lung bypass or other means. Adverse
neurological outcomes were observed only in 3.8% of surviving
patients, predominantly in those with arrest times longer than 30
min. The brain cooling methods described herein can be substituted
for the external cooling with ice baths during such procedures.
[0173] While "suspending" cerebral metabolism may explain some of
the protective effect of hypothermia, the temperature of the brain
at the time that cerebral blood flow is restored may also be an
important variable. This hypothesis is consistent with
reperfusion-injury theory. Neurological function may be better in
patients who have perfusion reinstated after cerebral cooling
rather than before cerebral cooling.
[0174] Clinical Indications
[0175] A variety of clinical conditions can be treated with the
methods, systems, and devices disclosed herein. In some
embodiments, the method involves determining whether a subject has
a condition that would benefit from treatment with the cooling
method and then treating the subject with the method once it has
been determined that the subject has that condition. In addition,
the method includes determining whether the condition would benefit
from relatively selective cooling of the brain or non-selective
cooling, then administering that type of cooling (or a combination
thereof). Examples of such conditions, and a treatment that can be
initiated in response to finding that condition, are shown in the
following Table 1.
TABLE-US-00001 TABLE 1 Clinical Indications for Cooling, and Types
of Cooling Selective cooling (targets cooling primarily the head
and brain) Anoxic encephalopathy Cardiac arrest Hemorrhagic shock
Sepsis Neonatal anoxic encephalopathy Stroke Embolic Hemorrhagic
Head trauma Closed Open Neurosurgery Cerebral aneurism repair
Hematoma evacuation Resection of abnormal tissue or tumor
Cardiovascular surgery CABG (Coronary Arterial Bypass Surgery)
Valve surgery CEA (Carotid Endarterectomy) Aortic aneurism repair
Pulmonary arterial embolectomy High risk general surgery Procedures
with risk of diminished oxygen or blood flow to brain from Hypoxia
Hypotension Systemic or cerebral embolization SIRS (systemic
inflammatory response syndrome) Status epilepticus Fever associated
with: Systemic infection Stroke Seizures Malignant hyperthermia
Neuroleptic syndrome Encephalitis Infectious Toxic Metabolic
Meningitis Prevention of hospital acquired pneumonia Non-selective
cooling (also targets cooling organs outside of the head) Early
stage of brain cooling Spinal cord Injury Ischemia Myocardial
infarction Cardiogenic shock SIRS (systemic inflammatory response
syndrome) Septic shock Hemorrhagic shock, large volume transfusion
Anaphylactic shock Acute lung injury ARDS (adult respiratory
distress syndrome) Aspiration Pneumonia TRALI (transfusion related
acute lung injury)
[0176] Treating Stroke:
[0177] Many animal studies have shown that cerebral cooling results
in improved neurological function and reduced volume of infarct
after stroke. Cerebral cooling appears to be beneficial even if
initiated hours following the onset of the stroke; however, more
benefit is obtained if therapeutically effective hypothermia is
promptly induced and maintained in accordance with the methods
disclosed herein. Cerebral cooling can be used as a primary therapy
for stroke, and can also be used as a bridging therapy before
attempting cerebral revascularization.
[0178] Cerebral revascularization is performed as a standard
treatment for embolic strokes. Thrombolytics are routinely used to
treat embolic stroke in patients who present to a medical center
within 3 hours of initial symptoms. The mechanical removal of
cerebral vascular embolism (embolectomy) has been shown to improve
neurological function in humans after stroke even if
revascularization is delayed until up to 8 hours after the onset of
the stroke. Timely revascularization is also combined with the
disclosed methods of rapid induction of cerebral cooling to
significantly improve neurological outcome after stroke.
[0179] Fevers:
[0180] High fevers are commonly seen in infection, stroke,
seizures, trauma, and adverse drug reactions. Fevers are associated
with significantly worse neurological outcomes. Current methods of
cooling are often not able to prevent or blunt fevers even when
patients are closely monitored in intensive care settings. Fevers
often present rapidly (spike) and often last for only 1-2 hours,
and current methods of cooling are not able to lower temperatures
significantly in this short amount of time, even when the brain is
normothermic and would be expected to take even longer to cool the
brain during fever. The methods disclosed herein are capable of
reducing cerebral temperatures to <33.degree. C. in 5-15 minutes
even in the face of fever to rapidly blunt fevers and reduce damage
to vulnerable organs such as the brain, lungs, and kidneys. Rapid
interruption of fever spikes is also believed to improve outcomes
in systemic inflammatory conditions, such as septic shock and acute
lung injury.
[0181] Surgical Procedures:
[0182] Brain damage is also a risk associated with neurosurgical,
cardiovascular, and other surgical procedures. Cognitive and
behavioral changes are common after CABG (coronary arterial bypass
surgery). Episodic hypotension and hypoxia are common occurrences
in such high risk surgical procedures. Surgical interruption of
cerebral blood flow is also required for cerebral aneurism repair
and CEA (carotid endarterectomy), which can induce transient or
permanent neurological damage. Cerebral hypothermia is believed to
reduce the effects of surgically-related brain damage from
intraoperative hypotension, hypoxia, interruption of cerebral blood
flow (emboli, vascular clamping), or inflammation. Brain cooling
before injury results in better outcomes than if cooling is
initiated after injury; therefore, to prevent or minimize
surgery-related brain injury, cooling is preferably completed
before the initiation of surgery, for example, between the
induction of anesthesia and the beginning of surgery. Cooling can
be maintained during surgery and the recovery period.
[0183] Myocardial Infarction and Ischemia:
[0184] The disclosed rapid induction of therapeutic hypothermia is
also believed to be advantageous in subjects who have had a
myocardial infarction (MI) whether or not blood flow is
reestablished to the affected area. If perfusion is not
reestablished, cooling is believed to limit the volume of dead
tissue by salvaging the areas with collateral circulation and
partial perfusion. Cooling the heart and systemic arterial blood
before perfusion is reestablished is believed to decrease
reperfusion injury, which may be the primary cause of permanent
myocardial damage after MI. In some embodiments of the method,
cooling is therefore initiated before revascularization and is
continued during and after coronary instrumentation or
thrombolysis. Rapidly induced hypothermia cools the heart in a
clinically desirable amount of time while reperfusion efforts are
underway. Rapid myocardial cooling occurs because cooled blood
occupies all four chambers of the heart, cooled systemic arterial
blood supplies the myocardium, and the outer surfaces of the heart
are directly cooled by the cold liquid in the esophagus and/or the
stomach.
[0185] The disclosed cooling methods are safe for use during
treatment for acute MI. Cardiac arrythmias are common after MI, and
systemic hypothermia increases the risk. It is therefore possible
that electrical cardioversion will be required to offset such heart
rhythm abnormalities; however, cardioversion can be performed
safely since the chest and torso will be dry, and the device is
electrically isolated.
[0186] Cooling of the Spinal Cord or Body to Diminish
Biflammation:
[0187] The disclosed method can also be used for non-specific
cooling of organs other than the brain. For example, irrigating the
oropharyngeal cavities and esophagus with cool water can be used to
cool the entire neck or back and adjacent structures, such as the
spine and spinal cord (such as the cervical spine) in a trauma
victim with a neck or back injury. Such cooling will diminish
residual adverse neurological sequelae. Although the spinal cord is
thinner than the brain, it is surrounded by more insulating tissue
and bone. These insulating features can be overcome, however, by
cooling the blood that is perfusing the spinal cord and its
surrounding structures. The regioselective features of the
disclosed method can be used to enhance treatment of particular
types of injuries, or maximize the cooling of specifically affected
areas.
[0188] Generalized cooling of the spinal cord can be achieved by
rapid and significant cooling of the brain, which lowers the
temperature of the cerebrospinal fluid (CSF) that circulates around
the spinal cord. The introduction of cool liquid through the tubes
in the mouth and esophagus will introduce a high rate of heat
convective transfer as flow contacts tissues that are very near the
brainstem, which can also be helpful in cases of basilar stroke or
other injuries to the brainstem. In addition, the cooling of blood
returning from the head (for example, via the jugular veins) in
turn cools the blood in the heart that is subsequently pumped
through the aorta and to the vertebral arteries that perfuse the
spinal cord. Cooling of the mediastinum by introducing cool liquid
into the esophagus and the stomach will cool the blood returning to
the heart via the superior and inferior vena cava. This cooled
blood will then be pumped to the spinal cord. The overall reduction
in body temperature achieved by lowering the temperature of aortic
blood also helps reduce the inflammatory response and minimize
permanent neurological damage that may otherwise occur to neuron
bodies from damage to its neurons.
[0189] Although regioselective cooling of the upper aerodigestive
tract will target cooling directly to the cervical spine, more
generalized cooling can be used to minimize systemic inflammatory
effects of trauma to the brain or non-brain structures (such as
spinal cord injury or other types of trauma, such as multiple
fractures). Complete submersion of the head accompanied by cooling
irrigation of the entire aerodigestive tract (but not the lungs)
will maximize total body cooling and accelerate induction of
protective cooling to minimize the inflammatory response. For
example, placement of irrigation tubes into the nasopharynx,
oropharynx, and esophagus (and optionally the stomach) will rapidly
induce widespread body cooling.
[0190] In cases of potential spinal injury, care must of course be
taken to stabilize the spine during the induction of rapid brain
and/or body cooling. Devices and methods that avoid extension of
the neck are preferred in such circumstances.
[0191] The disclosed methods cool the spinal cord at all levels
relatively rapidly because the cord is thin and of low mass.
Cooling of the upper cord is enhanced because it is bathed with
cold cerebrospinal fluid (CSF) from the cranium and direct cooling
from the upper airway. Cervical spine cooling is targeted for
33.degree. C. within 15-30 or 15-20 minutes of initiating
cooling.
[0192] Lung Cooling:
[0193] Inflammation associated with lung injury, such as the adult
respiratory distress syndrome (ARDS) has been extremely difficult
to prevent and treat. Broad anti-inflammatory modulation with
steroids has had mixed results and is not recommended for
early-stage ARDS. The only targeted anti-inflammatory therapy for
sepsis that has come to market is so toxic that it is
contraindicated in patient with isolated ARDS and no other organ
failure, the morbidity and mortality associated with the drug is
greater than that of ARDS alone. In contrast, systemic hypothermia
causes less toxicity while demonstrating broad anti-inflammatory
properties. Prior studies have shown that cooling in ARDS provides
a 33% reduction in predicted mortality when body temperature is
reduced to 33.degree. C. in severe ARDS otherwise refractory to
non-cooling treatments.
[0194] The lungs cool more quickly than most other organs
(including the brain) when the non-selective cooling methods
disclosed herein are used. The lungs have the greatest ratio of
blood flow to organ mass in the body, and the full cardiac output
runs through them. The lungs are also insulated by air in the
airspaces, which compose the majority of the lung's volume, and
have a low metabolic rate.
[0195] Avoiding Hospital Acquired Pneumonia:
[0196] Hospital acquired pneumonia, particularly for a patient
receiving mechanical ventilation, is caused by translocation of
bacteria from the upper airway to the lung. Currently, prevention
of ventilator associated pneumonia relies on attempts to disinfect
the upper airway using an antibacterial mouth wash applied twice
daily in combination with frequent oral care. However, the
disclosed cooling is believed to lower the incidence of ventilator
associated pneumonia by reducing the number of viable bacteria in
the upper airway by washing away bacteria with the large volume of
cooling liquid that passes through the upper airway. The
temperature of the cooling liquid renders the bacteria inert and
can even kill many species. In addition, cooling liquid that
contains propylene glycol further reduces the number of viable
bacteria because propylene glycol has broad antibacterial
properties.
[0197] Inhibiting Flow of Cool Liquid into Lungs
[0198] Maintaining the lungs free of the cooling liquid avoids loss
of the liquid from the upper airway and helps maintain more
effective gas transport in the lungs. A variety of techniques are
disclosed as means for inhibiting the entry of the cool liquid into
the lungs.
[0199] For example, the subject's head and neck may be extended
unless contraindicated (for example, when cervical spine damage is
suspected). Head and neck extension reduces the risk of cold liquid
entering the lung by elevating the level of the entrance of the
trachea (the larynx) compared to the level of the liquid.
[0200] Alternatively, the subject is placed in the Trendelenburg
position with the head lower than the chest. This position reduces
the risk of cold fluid entering the lung by elevating the level of
the entire trachea and lungs compared to the level of the
liquid.
[0201] Another possibility is to elevate the subject's chest on a
firm (possibly padded) board approximately 10 to 30 cm thick. The
chest elevation raises the level of the entire trachea and lungs
compared to the level of the liquid. In some embodiments, the board
will have a defect in the midline of the cephalad portion to allow
the neck to hyperextend without impingement on the board. The board
may also extend under the head at a thickness of 2 to 6 cm,
positioned under the box to support the box. The board can be firm
enough to support CPR.
[0202] As shown in the detailed embodiments of the method, a
multi-lumen endotracheal tube with an inflatable balloon cuff (or
for infants potentially without a cuff) may also function to keep
cold liquid from entering the lungs. The endotracheal tube may also
contain a third lumen with the distal opening immediately proximal
(above) the inflatable balloon cuff and with the proximal end
connected to suction. This third lumen can assist in removing
liquid proximal to the balloon cuff, reducing the amount of liquid
that would need to be blocked by the balloon cuff.
[0203] Liquid Flow and Temperature
[0204] The total amount of liquid introduced into the cool liquid
reservoir (if one is used) can be varied according to the needs of
the patient. As already noted, the cool liquid can be introduced at
a depth that covers the entire head and face. Another option is to
keep the liquid level below the level of the endotracheal balloon.
The pump flow (from one or more pumps) can be adjusted to provide
overall liquid flow in the range of 0.2 to 10 or L/minute to the
internal catheters (not including the catheters provided for
directing a flow of cooling liquid against the scalp of other
structure that does not involve insertion of a catheter into the
mouth or nose). In certain examples, this flow is at least 10
L/min, and in particular examples, a total flow of about or up to
20 or 30 L/min. The total flow is typically delivered through 1-6
(such as 2-6) or more catheters. The position of inflow and outflow
catheters can be changed over time if needed to provide or maintain
liquid flow over the scalp and in the upper airway.
[0205] In certain embodiments, flow can be adjusted to be 0.2-10
L/min into the upper airway and 1-20 L/min on the scalp for adults,
less for children and infants. A particular reservoir (such as a
box in which the head is partially or totally immersed) has a total
volume of about 40 liters if the box is about 35 cm on all sides.
In such particular embodiments, 1 to 15 or 20 total liters of cold
fluid are present in the reservoir, for example, about 10 liters.
The contents of the reservoir can be circulated about twice a
minute, or more, to achieve a desired degree of convection that
enhances head cooling. To maintain very high flow cooling at a low
temperature, even larger reservoirs of cooled liquid can be
employed, such as reservoirs that contain 20 or more liters (for
example, at least 30 or 40 liters) of the cooling liquid at the
desired temperature (for example, less than 5.degree. C., 0.degree.
C., -5.degree. C., or less).
[0206] To achieve optimal cooling, different flow rates of cooling
liquid can be introduced through different catheters that are used
in the method.
[0207] The temperature of the liquid in the container can be
adjusted by various cooling means over time when a container is
used. Similarly to flow rate, different cooling fluid temperatures
can be introduced through different catheters. For example, any one
or combination of the following methods may be used to adjust
temperature: [0208] adding cold liquid to the reservoir to increase
the volume of liquid in the box [0209] removing an aliquot of
warmer liquid and replacing it with colder liquid [0210] placing
inert cold objects within the reservoir [0211] placing frozen water
(water ice) or CO2 (dry ice) within the reservoir (as used herein,
"ice" refers generically to a solid phase of a non-metallic
substance that is a liquid or gas at room temperature) [0212]
placing a heat exchanger in series with the reservoir and the
pump
[0213] Additional air may be added to the balloons of the
endotracheal tube and the esophageal catheter to compensate for
volume loss in the balloon as the air within the balloon is
cooled.
[0214] The initial temperature of the liquid is in the range of -30
to +30.degree. C. Optimal temperature may vary during treatment but
is believed to be in the range of -20 to +10.degree. C.
[0215] The ideal cooling liquid is biologically compatible (for
example nontoxic) and has a melting point in the range of -50 to
+10.degree. C. and a boiling point of greater than 50.degree. C.
Examples of liquids meeting these are listed in Example 12. Liquids
can be combined or used in series during the treatment.
[0216] Multistage Cooling (Induction and Maintenance)
[0217] The cooling methods disclosed herein can be used for
multi-stage treatments, for example using induction and maintenance
regimens. In certain examples, the induction stage can take 15
minutes to an hour, followed by a maintenance phase that can last
greater than 12 hours, for example, 12-48 hours, such as up to a
week or more. It may be desirable to use different liquids and
temperatures in the induction and maintenance phases of the
treatment. For example, lower liquid temperatures will be used in
the induction phase to achieve more rapid cooling, while higher
liquid temperatures can be used in the maintenance phase. In one
example, the temperature of the cooling liquid during the induction
phase is -30 to 5.degree. C., while the liquid temperature in the
maintenance phase is 5 to 30.degree. C. Liquid flow rates are also
varied depending on the stage of treatment
[0218] In one example, a liquid temperature below 0.degree. C. is
used for the induction phase to achieve more rapid cooling (for
example during the first 30 minutes to one hour of cooling).
Temperatures below 0.degree. C. are achievable with liquids such as
propylene glycol cooled with ice. After cooling induction, higher
temperatures (above 0.degree. C.) are used for maintenance. Such
temperatures are readily achieved with cooled water.
[0219] Given the urgency of cooling the subject quickly to achieve
maximal benefit from the procedure, less controlled conditions may
be used during rapid induction, for example in the field (such as
in an ambulance) before a subject is brought to a hospital. Hence
the subject's head may be partially or completely immersed in a
container of ice water by emergency medical technicians who have
been sent to retrieve a patient who may benefit from the treatment.
The liquid in the container can also be used to supply the
irrigation fluid for the aerodigestive tract at a less controlled
temperature than would be achieved in the more controlled
in-patient setting (as in an intensive care unit).
[0220] Different body regions can also be cooled in different
stages of the treatment. Portions of the head and aerodigestive
tract that are suitable for irrigation with forced flow of cold
liquid include external structures such as the scalp and face, and
internal structures of the aerodigestive tract such as the
naso-pharynx (through nose tubes), the oro-hypopharynx (through a
mouth tube), the esophagus (through one or more esophageal tubes),
and the stomach (through a stomach tube). During induction, when
rapid cooling of the brain and/or body is desired, all regions may
be used for cooling unless otherwise contraindicated.
Alternatively, during induction catheters can be placed in all
these locations except the stomach. During maintenance treatment,
any combination of the external and internal structures can be used
to achieve desired degrees of targeted or non-targeted cooling.
[0221] Selective and Non-Selective Cooling
[0222] The disclosed method and device can be used to
preferentially or selectively cool the brain ("selective mode") or
to cool the entire body ("non-selective mode").
[0223] In the selective mode, the aerodigestive regions to be
cooled by applying cooling liquid are only the nasopharynx and
oropharynx, in some embodiments the cooling liquid is also
introduced into the upper esophagus. Liquid may optionally be
inhibited from entering the lower esophagus and the stomach by
placing an esophageal balloon that obstructs the lower esophagus.
However, in some embodiments of selective cooling the esophagus is
not mechanically obstructed.
[0224] In non-selective mode, the following regions are cooled:
scalp, face, nasopharynx, oropharynx, and portions of the
gastrointestinal tract, such as one or more or all of the upper
esophagus, lower esophagus, and stomach.
[0225] Selective cooling allows for lower temperatures in the brain
with less cooling of the body core and therefore less systemic
toxicity. In animal models, brain temperatures of 15.degree. C.
have been shown to be very well tolerated and therapeutic, while
core body temperatures of <30.degree. C. are associated with
increased risk of cardiac arrythmia, pneumonia and electrolyte
shifts. However, even very deep cooling to temperatures as low as
25.degree. C., or even 20.degree. C., does not appear to have
adverse effects in the brain. Benefits of cooling are likely a
non-linear function of cooling depth because cooling decreases the
metabolic rate of the cells, which in turn decreases both oxygen
demand and heat production in the tissue, as well as reducing
swelling and the rates of the other biochemical reactions
associated with re-perfusion injury.
[0226] Non-selective cooling is used to reduce the effects of
inflammation and ischemia throughout the body. Many diseases or
conditions are driven by inflammation: reperfusion injury after
organ ischemia, septic shock, trauma and allergic reactions.
Cooling has a potent broad non-selective anti-inflammatory effect
and is currently being studied as a treatment for some of these
conditions.
[0227] Cooling outside of the cranium is accomplished by cooling
the arterial blood supplying the organs or structures of interest,
or the body in general. Experimental data from use of the disclosed
device and method have demonstrated significant cooling of the
aortic blood, at approximately the same rate and depth as that of
the brain, even without cooling the lower esophagus or stomach.
Arterial blood temperature (measured in the aorta) is decreased by
profoundly cooling the blood returning to the heart from the head
and neck. Cooling of the face and scalp cools the blood delivered
to the extracranial structures of the head via the external carotid
artery. In addition, cooling of the tissue surrounding the upper
aerodigestive tract (above the esophagus) also cools the returning
jugular venous blood. Cooling of every possible surface of the head
and the entire upper airway provides effective non-selective
cooling.
[0228] Cooling structures below the upper aerodigestive tract, such
as the lower esophagus and stomach, increases the rate of systemic
arterial blood cooling. Cooling of the entire mediastinum can be
achieved by cooling the full length of the esophagus as well as the
stomach. The proximity of the esophagus to the superior vena cava,
right atrium and inferior vena cava allows for cooling of blood
coming from all areas of the body. Therefore, cooling of the entire
esophagus and the stomach allows for more rapid cooling of systemic
arterial blood by cooling all venous blood as it returns to the
heart.
[0229] Although some currently available hypothermia devices rely
on non-selective cooling, they are unable to provide non-selective
cooling at therapeutically beneficial rates. The methods and
devices disclosed herein are optimally able to achieve a
therapeutic target temperature in the brain within 5-10 minutes,
but optimal cooling of most of the non-brain organs is expected to
require more time. The rate and depth of cooling of an organ will
depend on multiple factors, including the organ's mass, metabolic
activity, rate of blood flow and cold induced vasoconstriction in
addition to the temperature of the blood perfusing the organ. This
amount of time is still much less than that required by
state-of-the-art devices, which require 3-6 hours.
[0230] The methods and devices disclosed herein are also capable of
delivering a rapid "burst" of hypothermia to affected organs (such
as the brain) early in the course of treatment. Rapid induction of
hypothermia allows for a more definitive reduction of inflammation
at the beginning of the inflammatory cascade, which is believed to
significantly enhance the effectiveness of treatment. Early
temperatures in target organs could briefly be obtained that are
far lower than what would be considered toxic if maintained
throughout the body for a prolonged period of time. Such rapid
cooling can comprise the introduction of cooling fluid for short
durations at pre-determined temperatures to achieve desired
treatment effects in much shorter periods of time (e.g., 6 hours, 5
hours, 4 hours, 3 hours, 2 hours, 1 hour, or less) than traditional
devices.
[0231] Any "overshoot" of systemic cooling can be rapidly
corrected. Since continuation of cooling requires continued use of
the device, merely discontinuing or diminishing treatment will
result in an increase in body temperature. This rapid reversibility
contrasts to other state-of-the-art devices which require warming
of the entire mass of the body if the core body temperature
decreases to an unwanted level. Warming the entire mass of the body
is a slow process. If still more rapid warming were desired,
external warming could be applied.
[0232] In certain embodiments of the method, therapeutic
hypothermia (e.g., to a core temperature range of approximately
33.degree. C. or less) is induced non-selectively followed by
selective cooling (for example, of the brain to result in very
rapid cooling of the brain). Delivery of warm blood from the body
via the carotid and vertebral arteries normally counteracts
cerebral cooling. However non-selective cooling results in a rapid
decrease in systemic arterial blood temperature, resulting in
cooler blood entering the carotid and vertebral circulations in the
upper chest and allowing for an even lower temperature of blood as
it enters the brain. Non-selective cooling also decreases the
minimum plateau temperature achieved in the brain. The minimum
temperature of the brain is a balance between the amount of heat
delivered to the head from the body and the amount of cold
delivered by the device. Since non-selective cooling decreases
systemic arterial blood temperature, less heat is delivered to the
head and lower brain temperatures are possible, and are more
rapidly achieved.
[0233] After the brain has reached its goal temperature (directly
measured or predicted by non-invasive measurements) cooling can be
switched from non-selective cooling to selective head cooling. This
change helps avoid adverse reactions from body core hypothermia.
After selective cooling is initiated, body warming can be initiated
to slow or reverse the temperature decline for the body core.
Warming can also be applied to the body core to hold the body at
one temperature while cooling is used to drive the brain to a lower
temperature.
[0234] Emergency Cooling with Rapid Induction
[0235] An advantage of the disclosed methods and devices is that
they are capable of inducing rapid cooling of the brain and/or
other organs and/or the entire body. Such rapid cooling has been
found particularly beneficial in the avoidance of permanent tissue
damage and the promotion of full functional recovery. Certain
disclosed embodiments can therefore be useful in connection with
emergency medical technicians (EMTs) in the field, for example, for
use by EMTs in ambulances transporting patients to a hospital.
[0236] A cooling unit (such as a small freezer) may be placed in an
ambulance, and the unit contains 5-50 liters of a cooling liquid
(such as 20% propylene glycol in water). If the technicians find a
subject who has a condition that would benefit from brain and or
body cooling (as detailed in other sections of this specification),
then rapid field-induction of brain or body cooling can be achieved
by quickly immersing the head of the patient in cooling liquid. To
simplify use of the device in the field, ice cubes can be placed in
the liquid to maintain it at the desired temperature. The iced
liquid in which the head is submerged also serves as a reservoir of
cooling liquid that can be directed in a flow externally against
the head, and/or used as an irrigating fluid for introduction into
the aerodigestive tract. This simple version of the device will not
require any electrical cooling devices, and cooling can be
maintained by ice cooled liquid alone for the duration of
transportation of the patient to the hospital.
[0237] When used in the field, and to simplify the technique for
rapid induction and ease of transportation, the cooling of the
aerodigestive tract may be carried out without external application
of cooling liquid to the head, as would occur in partial or total
immersion of the head. However, the cooling liquid may optionally
be applied externally to the head to further accelerate rapidity of
therapeutic hypothermic induction.
[0238] Pump Embodiments
[0239] Multiple pumps can be incorporated into the system. For
example, a first pump can draw liquid 118 from the reservoir in
container 112 through a first inlet conduit to the first pump and
pump the liquid back through a first return conduit into container
112 externally over the head. A second pump can draw liquid from
the same reservoir through a second inlet conduit to a second pump
and pump the liquid back through a second return conduit to the
upper airway catheters. An advantage of the separate pumps is that
the flow of liquid can be separately regulated if external delivery
around the head is desired and for internal delivery into the upper
airway. This is a particular advantage when the caliber of the
upper airway catheters is different than the conduit for external
delivery of the liquid, and the internal resistance of the external
and internal delivery systems differs.
[0240] In other embodiments of the method that use multiple
catheters, each catheter can be associated with a separate pump.
Alternatively, a separate pump can provide liquid flow to all
catheters in particular anatomic regions, such as all the external
catheters, all the internal catheters, all the catheters in the
upper airway, all the catheters in the gastrointestinal tract
(esophagus and/or stomach), etc.
[0241] Various types of pumps can be used with the present
invention, such as, for example, peristaltic pumps (e.g., to permit
pumping fluid without contacting the fluid), diaphragm pumps (e.g.,
with disposable heads), and/or gear pumps (e.g., with disposable
heads).
[0242] The pump or pumps may be either manually operated or
non-manually powered, for example by electricity. A hand or foot
powered pump can be used for field operation outside a hospital or
ambulance where a source of electricity may not be readily
available. Once the patient is transported to an ambulance or
hospital, the pump can be connected to a source of electrical
energy and automated pumping initiated and continued for a
sustained period of time.
[0243] Batteries can also be used to power the pump for field
operation.
[0244] Esophageal Tubes
[0245] A variety of specialized single or multi-lumen esophageal
tubes can be provided to deliver the high flow of cooling liquid to
the aerodigestive tract in those embodiments that employ esophageal
irrigation. For example, a single, double, triple, and/or quadruple
lumen catheter may be employed.
[0246] With a triple-lumen catheter, the inner lumen, for example,
can be the longest and can provide stomach access. In some
instances, the lumen acts as a nasogastric tube hooked up to
suction, for example, to remove cooling and other liquids from the
stomach if desired. Alternatively, the long inner lumen can be used
to deliver cooling liquid to the stomach. The middle lumen can, for
example, deliver cooling liquid and can have multiple side ports
for omni-directional delivery of the cooling liquids in multiple
different directions and at different levels of the esophagus. In
other embodiments, the middle lumen can be configured to permit air
and/or liquid to pass to an inflatable member (e.g., a cuff) to
permit inflation of the member. The outer lumen can selectively
remove cooling liquid from the esophagus if desired (e.g., via a
negative pressure device in fluid communication with the outer
lumen). In other embodiments, similarly to the middle lumen
described above, the outer lumen can be configured to permit air
and/or liquid to pass to an inflatable member (e.g., a cuff) to
permit inflation of the member. However, flow of returning liquid
moving along the wall of the esophagus toward the mouth is helpful
in achieving heat transfer to the liquid, hence suctioning of
return liquid is not normally used absent special
circumstances.
[0247] Alternatively, multiple parallel tubes of different lengths
can be used to introduce flow into the esophagus. The longest tube
can be positioned with its tip in (or near) the stomach and can
serve to introduce cooling liquid to the stomach, suction cooling
liquid from the stomach, and/or provide pressure relief from the
stomach. This tube can have an inflatable balloon around the tube
(e.g., about 10 cm from the distal end of the tube). The balloon
can selectively be inflated in the lower esophagus if it is desired
to isolate the stomach from the flow of liquid in the esophagus so
that the cooling liquid is directed more selectively to the
esophagus. The mid-length tube can be of a sufficient length to be
positioned with its tip near the inflatable balloon (e.g., about 3
cm from the balloon on the first tube). In some embodiments, the
mid-length tube can comprise one or more side ports for the
delivery of the cooling liquid and/or suction of cooling liquid
(e.g., depending on the embodiment). The short tube can be
positioned with its tip in the hypopharynx, and, similarly to the
mid-length tube, can have one or more side ports along its length
for delivery and/or removal of cooling liquid in the hypopharynx.
Endotracheal catheters can comprise similar features to the
esophageal catheters described above while being configured to be
disposed in a patient's trachea.
[0248] Mouth and or Nose Drainage
[0249] An advantage of certain embodiments of the device and method
is that the cooling liquid is capable of draining passively through
the mouth and/or nose without application of suction. Removal of
liquid through the mouth and/or nose avoids removal through suction
tubes placed in the aerodigestive tract, and therefore provides
flow of the cool return liquid over the large surface area of the
tissues of the aerodigestive tract to maximize heat exchange
between the tissues and the liquid. Drainage of the liquid through
the mouth and/or nose can be achieved with the head entirely
submerged in the cooling liquid, partially submerged in it, or not
submerged at all.
[0250] In some illustrated embodiments, liquid that drains out of
the mouth collects in a reservoir around the head. However, the
draining liquid can also collect in a reservoir that is below or
beside the head. For example, the head may be supported by a
permeable support surface having an opening or openings through
which liquid returns to the reservoir. The draining liquid can then
be cooled and returned to the aerodigestive tract for continued
cooling of the tissues.
[0251] In one example, the head may be turned to the side so that
liquid will pour out one side of mouth, which will help avoid
contacting the cool liquid with the face and help keep liquid out
of the lungs by lowering the level of liquid in the upper airway.
The head can be gently restrained to keep the head turned to its
side, and the corner of the mouth may be pulled down to encourage
egress of liquid from the mouth. In some embodiments a drainage
tube can be place in the mouth to further reduce the level of
liquid in the mouth. Or the liquid can be primarily withdrawn by
suction (e.g., via a negative pressure device through one or more
endotracheal and/or esophageal tubes), in this case the open mouth
and nose serve as a "safety outlet" preventing any increase in
pressure.
[0252] Cooling Liquids
[0253] A variety of biologically compatible cooling liquids can be
used, either alone or in combination, in the disclosed methods and
devices. A biologically compatible liquid is one that is either
non-toxic, or that has levels of toxicity that are acceptable in
view of the problem being treated. Some toxicities are minor (such
as skin irritation that can be caused by glycerol), and others are
more significant (such as causing electrolyte abnormalities) but
can be medically managed. As long as the toxicity presented by use
of the liquid is acceptable in the clinical circumstances in which
it is used, the liquid is considered biologically compatible. Any
liquid that causes a severe permanent injury or is incompatible
with life is not considered biologically compatible. Liquids that
may not be biologically compatible at high concentrations can in
some instances be made biologically compatible by adding a diluent
(such as water).
[0254] Examples of biologically compatible liquids are listed in
Table 2.
[0255] Cooling liquids particularly useful in the methods disclosed
herein have high heat capacity and thermal conductivity. Gases are
not suitable for this purpose because they do not transfer heat at
the rate envisioned by the disclosed methods. The optimal
temperature for a particular liquid is often the lowest temperature
that can be achieved without freezing, and with an acceptable
degree of viscosity.
[0256] Colder cooling liquids increase the rate of brain and/or
body cooling, however the rate of cooling is balanced with the
potential tissue damaging effect of the cold liquid. However,
animal (including human) tissue can tolerate surprisingly low
temperatures, at least for limited periods of time. Items from food
freezers (-17.degree. C.) are routinely placed on skin after trauma
to reduce swelling, which illustrates the ability of skin to
tolerate such low temperatures. The mucous membranes (such as those
found in the aerodigestive tract) also tolerate low temperatures,
as illustrated by the fact that items from food freezers
(-17.degree. C.) are routinely eaten.
[0257] Mixtures of liquids are particularly contemplated as useful
in the disclosed methods. For example, mixtures that take advantage
of interactions with water can be used. A water/propylene glycol
mixture is a preferred liquid for induction because it can be
cooled to temperatures below 0.degree. C. A water/saline cooling
liquid will likely be used as maintenance liquid to maintain a
temperature above 0.degree. C. for 12-48 hours because of its low
toxicity. Saline solution has a lowered freezing point, and is
easily washed off the patient, staff and equipment.
[0258] Examples of cooling liquids include those shown in Table
2.
TABLE-US-00002 TABLE 2 Cooling Liquids Water-based Propylene glycol
(5-25% in water) Ethanol (5-25% in water) Glycerol/glycerine (5-25%
in water) Dextrose (5-25% in water) Sodium chloride (1 to 5% in
water) Calcium chloride (1-25% in water) Oils High-oleic safflower
oil Corn oil Castor oil Perfluorocarbons Perfluorohexane
Perfluoroheptane Perfluorooctane Additives (optional) Detergents
(trace)
[0259] Trace quantities of detergents such as sodium laurel
sulfate, sodium laureth sulfate, etc can be added to the cooling
liquid to solubilize debris and bodily fluids (blood, mucus, hair,
sweat) and inhibit pump/tubing obstructions.
[0260] As mentioned above, a particularly preferred cooling liquid
for the induction phase is propylene glycol (PG) and mixtures of PG
in water. The PG is cooled to -10 to -20.degree. C., and is used
during induction for 30-60 minutes. This temperature is achievable
because PG 40% in water has freezing point of -22.degree. C. PG is
in an FDA classification of "generally recognized as safe" and has
very low ingestion toxicity. For example, PG is found in high
concentrations in foods and cosmetics; the average adult in the
United States consumes 2.5 grams/day of PG in food. PG is a common
ingredient in mouthwash, and is the main ingredient in many oral
and intravenous medications. It causes minimal skin and eye
irritation, and is used in many topical medications and personal
care products. PG has been nebulized and inhaled for treatment of
chronic lung disease. It is easily flushed off mucous membranes and
skin by water or saline, so this induction liquid can easily be
removed by flushing with saline, water of other liquid that is used
in a subsequent maintenance phase of treatment.
[0261] Other characteristics of PG that make it very suitable as a
cooling liquid are its high specific heat (which is close to water
and better than ethylene glycol), a viscosity only slightly higher
than water, a surface tension lower than water (when mixed with
water), compatibility with many types of flexible tubing and pumps,
very low flammability, and no special disposal needs.
[0262] A particularly suitable cooling liquid for maintenance of
hypothermia is saline solution, such as 0.9% saline solution. An
optimal temperature range for maintenance liquid is +5 to
+20.degree. C., and an example of a maintenance period would be
12-48 hours. Use of saline maintenance solution for this sustained
period of time is particularly suitable because it is considered a
"physiologic" fluid. Saline solution during maintenance therapy
also avoids dermal and enteral absorption of propylene glycol
during long-term use. Saline solution can be adjusted such that it
is osmotically neutral with the tissues surrounding the
aerodigestive tract.
[0263] Glycerol can be a particularly useful cooling liquid
component, because when added to water it has a low surface
tension. Salt in water (saline solution) has no effect on viscosity
and does not decrease surface tension. Sugar solution increase
viscosity of the liquid, while ethanol decreases surface tension
(but must be treated with caution because of its flammability).
Calcium chloride slightly increases the viscosity of a solution,
and it used in low concentrations because it can be an irritant at
very high concentrations.
Comparative Data
[0264] Comparative studies have been performed to compare cooling
induced by the method as described by Brown et al., Profound
Selective Cerebral Hypothermia in Dogs by Naso-Oral Perfusion and
Head Immersion, Surgical Forum 15:413-415, 1964 (Trial 1); improved
cooling with liquid at 0.degree. C. and scalp, nasal, oral and
upper esophageal cooling (Trial 2); cooling liquid at -15.degree.
C. using scalp nasal and oral cooling (Trial 3).
[0265] Surgical Preparation of the Animal
[0266] A 98 kg adult female sheep was maintained under surgical
plane anesthesia until euthanized. The sheep was subjected to 3
methods of cerebral hypothermia and outcome was measured by the
rate and magnitude of cooling of the superficial cortex of the
brain and of the systemic arterial blood. Temperatures were
recorded every minute in superficial cerebral cortex, in arterial
blood in the abdominal aorta, in the peri-carotid tissue of the
neck, in the rectum (core temperature), and in the device
reservoir. Monitoring was performed by continuous ECG, continuous
pulse oxymetry, continuous arterial blood pressure, and continuous
end-tidal CO2.
[0267] During surgical preparation, the sheep was intubated orally
with a standard cuffed endotracheal tube (ETT) and mechanically
ventilated with 100% oxygen and minute ventilation titrated to an
end-tidal CO2 of 35 Torr. Tracheostomy was performed and a cuffed
tube was placed with the tip in the lower trachea. Esophagostomy
was performed and a cuffed tube was placed with the tip in the mid
esophagus and the proximal end to gravity. Arterial and venous
catheters were placed in the right groin.
[0268] The left mid neck was dissected, a temperature probe was
placed lateral to the carotid artery and the site closed at the
levels of the fascia and the skin. The scalp was dissected in the
left upper parietal region, and a 10 mm burr hole was created
through 22 mm of skull. The dura and superficial brain were incised
and a temperature probe was placed with tip 7 mm below the surface
of the cerebral cortex. The burr hole was sealed with dental
cement. The site was closed at the levels of the fascia and the
skin and covered with petroleum jelly.
[0269] Catheters were obtained for use in the following examples.
The catheters had the following inner diameter (ID) and outer
diameter (OD): [0270] intake tubes--from reservoir to each of the 3
pumps [0271] ID=1/2 inch [0272] OD=3/4 inch [0273] scalp tubes
[0274] ID=1/2 inch [0275] OD=3/4 inch [0276] nasal and oral and
esophageal tubes [0277] ID= 5/16 inch [0278] OD= 7/16 inch
[0279] Trial 1--Selective Cooling with Low Flow Cooling Liquid from
Catheters Inserted Only into Nostrils (Brown et al. Method)
[0280] One tube was placed in each nasal cavity by inserting the
tip of the tube 5 cm beyond each nares.
[0281] A box open at the top acted as a reservoir for cooling
liquid. The reservoir was filled with water with ice at 0.degree.
C. A pump withdrew liquid from the reservoir at 1.8 L/min,
introduced it through the tubes into the nasal cavities. The liquid
returned passively back to the reservoir via the nose and mouth. At
the start of cooling the head was submerged in the reservoir by
tilting the surgical table head-down, removing the headrest from
the table and extending the neck. At the same time the nasal tubes
were connected to the outflow tube of the pump. Cooling was
discontinued after 30 minutes, the pump stopped, the head removed
from the reservoir and the sheep rewarmed using a warm saline IV
infusion and external warming of the trunk. Nasal tubes were left
in place and disconnected from the pump.
[0282] Cooling was performed for 31 minutes, then rewarming was
initiated. The data that was obtained is shown in Table 3.
TABLE-US-00003 TABLE 3 Selective Cooling with Low Flow Cooling
Liquid only into Nasopharynx Temperature (deg C.) Time (min) Brain
Peri-carotid Aorta Bath Core 0 38.1 37.8 37.7 1.3 38.1 1 38.1 37.8
37.6 1.2 38.1 2 37.8 37.7 37.1 1.5 38.1 3 37.4 37.7 36.8 1.7 38 4
37.1 37.7 36.6 2.1 37.9 5 36.7 37.4 36.3 2.2 37.8 6 36.3 37.4 36.2
2.5 37.8 7 35.9 37.1 35.9 2.5 37.7 8 35.9 36.8 35.9 2.7 37.5 9 35.9
36.8 35.4 2.8 37.4 10 35.6 36.5 35.3 2.9 37.3 11 35.3 36.4 35.3 3
37.2 12 35.3 36.2 35.3 3.1 37.1 13 35 36.2 35.4 3.2 37.1 14 35 35.9
35.4 3.2 37.1 15 34.8 35.9 35.3 3.4 37 16 34.8 35.9 35.1 3.4 36.9
17 34.8 35.7 35 3.7 36.8 18 34.6 35.7 34.5 3.7 36.8 19 34.3 35.4
34.5 3.7 36.6 20 34.3 35.4 34.7 3.8 36.5 21 33.9 35.4 34.7 3.9 36.5
22 33.9 35.3 34.6 4 36.4 23 33.9 35.3 34.1 4.2 36.4 24 33.9 35.1
34.1 4.2 36.3 25 33.9 35.1 34.1 4.4 36.2 26 33.7 35.1 34.1 4.5 36.1
27 33.4 34.9 34 4.5 36 28 33.4 34.9 34.1 4.7 35.9 29 33.4 34.7 34.1
4.8 35.8 30 33.4 34.7 34.2 4.8 35.8
[0283] Trial 2--Selective Brain Cooling
[0284] After rewarming the animal from the trial described in Trial
1, an oral tube was placed with the tip at the base of the tongue
and an esophageal tube was placed with the tip in the upper
esophagus. Two additional tubes were placed in the liquid
reservoir. When the head was submerged in the reservoir their tips
were 4 cm from and pointed towards the right and left parietal
scalp. A box open at the top acted as a reservoir for cooling
liquid. The reservoir was filled with water with ice at 0.degree.
C. At the start of cooling the head was submerged by tilting the
surgical table head-down, removing the headrest from the table and
extending the neck. Three pumps (1, 2, and 3) were used. The two
nasal tubes were connected to the outflow tube of pump 1, oral tube
to pump 2, esophageal tube to pump 2 and the two scalp tubes to
pump 3. Pumps withdrew cool liquid from the reservoir at 6 L/min
for pump 1, and 12 L/min each for pumps 2 and 3. Cooling was
discontinued after 21 minutes, the pumps stopped, the head removed
from the reservoir and the sheep rewarmed using a warm saline IV
infusion and external warming of the trunk.
[0285] Data obtained from the method is shown in Table 4.
TABLE-US-00004 TABLE 4 Selective Brain Cooling Temperature (deg C.)
Time (min) Brain Peri-carotid Aorta Bath Core 0 36.8 36.4 35.5 1.2
36.2 1 35.8 36.4 35.6 1.3 36.2 2 3 4 35.9 27.2 34.1 3.4 36 5 35.5
24 33.7 3.8 35.9 6 34.8 21.9 33.2 3.9 35.7 7 34.4 20.7 32.8 3.9
35.5 8 33.6 19.8 32.5 4 35.3 9 33.3 21.1 32.4 4.2 35.2 10 32.9 22
32.2 4.6 35 11 32.3 21.2 31.9 4.8 34.8 12 32 20.2 31.6 5 34.7 13
31.7 19.7 31.3 5.3 34.5 14 31.3 19.3 31.1 5.6 34.3 15 31.3 19.3
30.9 5.7 34.1 16 30.9 18.9 30.7 5.9 33.9 17 18 19 30.3 22.3 30.5
6.7 33.5 20 30 20.1 30.4 7.1 33.3 21 30 19.6 30.2 7.3 33.2
[0286] Trial 3--Propylene Glycol as Cooling Liquid (Trial 3)
Continued Cooling after Animal Euthanized (Trial 4)
[0287] After rewarming the animal from Trial 2, the esophageal tube
was withdrawn and replaced with a second oral tube, so that there
were two oral tubes both having their tips positioned at the base
of the tongue. Both nasal and both scalp tubes remained in place. A
box open at the top acted as a reservoir for cooling liquid. The
reservoir was filled with a 1:1 mixture of propylene glycol and
water at -15.degree. C. Pumps withdrew fluid from the reservoir at
1 L/min for pump 1, and 3 L/min for pump 2 and 5 L/min for pump 3
for a total of 9 L/min through the internally placed catheters. At
the start of cooling the head was submerged by tilting the surgical
table head-down, removing the headrest from the table and extending
the neck. At the same time the nasal tubes were connected to the
outflow tube of pump 1, oral tubes to pump 2, and the scalp tubes
to pump 3. Pumps withdrew liquid from the reservoir at 1 L/min for
pump 1, at 3 L/min for pump 2 and 5 L/min for pump 3 for a total of
4 L/min through the internally placed catheters and 5 L/min of
liquid was directed at the scalp.
[0288] The sheep was euthanized after 14 minutes and cooling
proceeded for another 22 minutes.
[0289] The results of the cooling with propylene glycol are shown
in the Table 5. Measurements after death are presented in bold
italics.
TABLE-US-00005 TABLE 5 Propylene Glycol as Cooling Liquid with
Continued Cooling after Animal Death Temperature (deg C.) Time
(min) Brain Peri-carotid Aorta Bath Core 0 34.6 34.7 33.9 -12.9
34.2 1 34.6 34.7 33.9 -11.6 34.2 2 34.3 31.7 33.2 -11.1 34.1 3 33.9
27.6 32.7 -9.3 34 4 33.4 25.4 32.4 -7.8 33.8 5 33.1 24.7 32.1 -5.9
33.6 6 32.6 25.1 31.8 -3.8 33.4 7 32.2 22.5 31.3 -2 33.2 8 31.8
23.1 31.3 0 32.9 9 31.8 22.4 31.1 0 32.7 10 31.4 21.9 31 0 32.5 11
31.1 21.6 31 1 32.3 12 31.1 21.6 30.9 1.4 32.3 13 30.8 21.4 30.8
2.3 32 14 30.8 21.5 30 2.8 31.9
[0290] Comparison of Aortic Blood Cooling Using Nasal Vs.
Aerodigestive Cooling
[0291] Aortic blood temperature data in the following table
illustrates the superior rate of systemic blood cooling achieved by
introducing the higher flow of liquid into multiple sites along the
aerodigestive tract and the scalp. Cooling would be accelerated
even more if lower esophageal and stomach catheters were added, and
cooling liquid introduced into the aerodigestive tract through them
as well. Cooling liquid is also accelerated by using cooling liquid
colder than 0.degree. C.
TABLE-US-00006 TABLE 6 Aortic Blood Temperature nasal + oral +
upper time (min) esophageal + scalp nasal + scalp 0 35.5 37.7 1
35.6 37.6 2 37.1 3 36.8 4 34.1 36.6 5 33.7 36.3 6 33.2 36.2 7 32.8
35.9 8 32.5 35.9 9 32.4 35.4 10 32.2 35.3 11 31.9 35.3 12 31.6 35.3
13 31.3 35.4 14 31.1 35.4 15 30.9 35.3 16 30.7 35.1 17 35 18 34.5
19 30.5 34.5 20 30.4 34.7 21 30.2 34.7 22 34.6 23 34.1 24 34.1 25
34.1 26 34.1 27 34 28 34.1 29 34.1 30 34.2
[0292] With regard to Trials 1-3, using pure water as the cooling
liquid, the addition of esophageal, oral irrigation, and scalp flow
to nasal irrigation more than doubled the rate of cerebral
temperature drop from 30 min to 13 min for a 5.degree. C. drop in
brain temp. A temperature drop of 5.degree. C. in 13 minutes is a
remarkable rate of cooling. Head cooling still has an effect even
without a pulse. After death of the animal, the core body and
aortic temperature actually increased but brain temp continued to
decrease. Hence the cooling liquid has a direct effect on the
brain, in addition to the effect of cooling blood in the vessels
that perfuse the brain.
[0293] Brain temperature also decreased significantly in Trial 3
despite two departures from optimal operating conditions. First,
the esophageal tube was not optimally placed because the tip
remained in the oropharynx in Trial 3 and served as a second oral
tube. Second, the high viscosity of the 50% propylene glycol in
water cooling liquid resulted in decreased flow rates of liquid
into the aerodigestive tract. A much deeper and more rapid
temperature drop would be expected with 20% PG and bath temperature
of -10.degree. C. because the viscosity would be lower and the flow
rates of the liquid in the aerodigestive tract would be
greater.
[0294] Nonetheless, the blood temperature achieved by adding
aerodigestive cooling to scalp cooling is substantially lower than
cooling merely the nasal cavity and scalp. Nasal+scalp cooling
reached a minimum temperature of only 34.degree. C. and
equilibrated, while the addition of aerodigestive cooling achieved
a blood temperature of 30.degree. C. and was still decreasing when
the experiment ended. This is a substantial difference; without
aerodigestive cooling the total temperature drop was 4.7.degree.
C., while with aerodigestive cooling the temperature was
3.4.degree. C. cooler in less time and had still not
equilibrated.
[0295] In Trial 3 with propylene glycol, brain temperature reached
a brain temperature of about 28.degree. C. in 32 minutes, even
though the experimental subject had been dead for about half that
cooling time. Previously published reports have reported reaching
temperatures of only about 33.4.degree. C. in 30 minutes. Hence the
aerodigestive cooling method is capable to cooling about twice as
quickly in the critical first 30 minutes during which therapeutic
hypothermia is being initiated.
[0296] The addition of esophageal flow helped increase the rate and
depth of cooling. There did not appear to be any significant loss
of cooling liquid into the stomach from the tube placed in the
esophagus. Greater esophageal distension from even higher
esophageal flow rates would be expected to increase the surface
area of the esophagus, and provide a greater esophageal surface
area for heat transfer to occur.
[0297] Since the sheep (98 kg) was larger than a typical human
adult (60-70 kg), had a skull much thicker than a human skull, and
possessed an effective boundary of fur despite close shearing, the
rate and depth of direct brain cooling provided by scalp cooling is
expected to be greater in humans. However, the inventor has
demonstrated a much more rapid rate of cooling is possible using
aerodigestive cooling as opposed to nasal cooling alone.
[0298] In some embodiments of the method in which more focal
hypothermia is desired (for example, selective cooling of the
brain) the body can be warmed, for example by wrapping the trunk
and extremities in heating blankets. The cooling methods disclosed
herein cool much more rapidly and deeply than previous methods by
cooling a combination of surfaces, and/or using very high rates of
flow of cooling liquid. The method is also versatile in that it can
be used for substantially specific cooling of the brain alone or
less specific cooling of the brain and other organs, either in or
remote from a hospital setting or in transit between those sites.
The method is capable of deeply cooling about 15% of cardiac blood
flow (the blood flow to the head), is non-invasive to the extent
that liquid is only introduced into the aerodigestive tract, and
can combine internal and external cooling.
[0299] All regions cooled are integrated by combining all return
liquid from the body, mixing and redelivering liquid to the body.
The return of cooling liquid from the body in the experiments was
passive, which allows for much higher flow of cooling liquid out of
the nose and mouth, and in turn provides more rapid cooling. The
simplicity of the equipment for carrying out the method allows for
rapid implementation and broad applicability, so that more people
can benefit from the simple sophistication of the approach. The
simplicity of design, in which the method can be performed without
inserting catheters into organs (such as the brain) leaves vital
organs intact and allows more people to benefit from its use. The
method and device can be used inside or outside a medical facility
so that patients do not have to wait until they reach the emergency
room to be treated. The method is suitable for use by less trained
medical personnel (such as EMTs) without having to wait for a
surgeon to arrive to perform invasive surgical maneuvers (such as
introducing cooling catheters into the brain or blood vessels).
[0300] The brain can also be maintained significantly colder than
the rest of the body during selective cooling, which maximizing
brain benefit and minimizes body side effects. Rapid cooling can be
induced much faster and attain much lower brain temperatures than
with conventional induction of therapeutic hypothermia using prior
art methods. In some examples, the temperature in the cerebral
cortex is lowered to 33.degree. C. in 5-15 minutes, or 28.degree.
C. in 10-20 minutes, or 25.degree. C. in 15-30 minutes. In other
examples, the temperature in systemic arterial blood is lowered to
33.degree. C. in 5-15 minutes, to 28.degree. C. in 15-30 minutes,
or to 25.degree. C. in 20-40 minutes.
[0301] A variety of different catheters/tubes can be used in the
devices. Specific, non-limiting examples of particular catheter
sizes are described above in relation to Trials 1-3. Examples of
ranges of catheter sizes are 5/16 to 1/2 inches ID for the scalp
tube, 3/16 to 6/16.sup.th inches for the esophageal and stomach
tubes, 3/16 to 1/2 inches for the mouth tube, and 2/16 to
6/16.sup.th inches for the nose tubes.
[0302] The method is also capable of rapidly inducing cooling by
using "stored cold" for the induction phase in the form of ice
water or pre-cooled liquids that are available for emergency use,
for example during the first 30 minutes of cooling. The temperature
of the cooling liquid is also quite low, and using cooling liquids
that are available at sub-zero temperatures to increase the rate
and depth of cooling. The volumes of cool liquid available in the
reservoir help maintain a sufficient supply for continued high
volume flow of cooling liquid.
[0303] Organs are cooled by cooling the blood that supplies the
organs, so that the disclosed methods do not require total body or
even regional cooling to be effective. For example, if cooling of
the cervical spinal cord is desired, this low mass region is
rapidly cooled without waiting for the much more massive contents
of the abdomen to be cooled.
[0304] The disclosed methods cool the head, neck and mediastinum
using simple but effective techniques to maximize heat transfer.
Selective cooling rapidly and deeply cools arterial blood delivered
to the brain via the carotid and vertebral arteries. Non-selective
cooling is capable of cooling venous blood returning to the heart,
and therefore the systemic arterial blood. The venous blood is
cooled in two regions, the neck and the mediastinum. The
temperature of the blood draining from the neck is very low, in
time approaching the temperature of the cold liquid bath that
bathes it. This is due to cooling of the blood in the head and neck
at the capillary level (most profound in the tissue beds in
proximity to the skin and mucus membranes that are in direct
contact with the cooling fluid) in addition to cooling of the blood
in the jugular veins via cold fluid in the upper airway. About 15%
of the cardiac output will be cooled in this very efficient
manner.
[0305] The esophagus traverses the entire mediastinum and is in
close proximity to the inferior vena cava, superior vena cava and
the heart. The vena cava carries the entire cardiac output back to
the heart. It is thin walled and lies in very close proximity to
the esophagus, allowing for very efficient heat transfer with the
esophagus. The stomach is in close proximity to the inferior vena
cava as well as the inferior surface of the heart.
[0306] Direct contact of cooling liquids with the aerodigestive
tract (as opposed to placing the liquid in a container within the
tract) allows for the full surface area of the aerodigestive tract
(from nares to pyloris) to be used for heat exchange. The cooling
liquid enters irregular areas of the surface that balloons or rigid
devices would not reach. Examples of such irregular surfaces that
are bathed with the cooling liquid are the nasal trabeculae,
tonsils, and larynx.
[0307] In addition to the convection due to flow of cool liquid
through the aerodigestive tract, forced flow of the cooling liquid
(both externally against the face and scalp and internally in the
aerodigestive tract) contributes to convective heat exchange. For
example, a thick layer of stagnant liquid at the outer aspects of
the esophageal lumen could cause the flow of cool liquid to flow
down only a central core that reduces heat exchange. Mixing can be
increased by having multiple points of liquid delivery (multiple
catheters and each catheter can have side holes), high flow rates,
crossed currents of liquid flow (liquid is pushed into the body and
generally directed towards the feet but changes direction and is
expelled out the mouth and nose), encountering irregular surfaces
in the aerodigestive tract (not smoothed over by a bag or balloon)
and the presence of multiple delivery tubes along the path of
liquid exit.
[0308] Another advantage of the method is that it is capable of
providing the internal delivery of the cool liquid to the
aerodigestive tract without immersing other parts of the body (such
as the chest, extremeties or even in the head in some embodiments)
in cooling liquid. Hence it is possible to perform other
interventions on the patient that would not be possible in other
types of induced hypothermia. Examples of such interventions
include electrical cardioversion (applying electrical energy to the
heart to change or initiate its rhythm), electrocardiography
(obtaining diagnostic signals from the heart by applying external
electrodes to the body, including the thorax), or performing
cardiac or neurovascular surgery (such as angioplasty or
stenting).
[0309] Temperature management devices and methods can be provided
to achieve more rapid cooling, more brain selective cooling, and
independent manipulation of brain and body temperature. The
temperature management devices and methods described herein include
methods of inducing and maintaining brain selective, systemic, and
combined brain selective and systemic temperature management (e.g.,
cooling and warming).
[0310] The systems and methods described herein can generally be
used in connection with one or more of the following
activities:
[0311] 1. Rapid Lowering of Brain Temperature, without Control of
Core Temperature.
[0312] Possible clinical uses of this include, for example,
treatment of cardiac arrest, MI, intraoperative organ protection,
head trauma, stroke, hemorrhagic shock, fever.
[0313] 2. Maintaining Brain Temperature Below Core Temperature
while Maintaining Core Temperature Near Normal.
[0314] Possible clinical uses of this can include, for example,
treatment of cardiac arrest, MI, intraoperative organ protection,
head trauma, stroke, and hemorrhagic shock.
[0315] 3. Maintaining Brain Temperature Below Core Temperature
while Maintaining Core Temperature Below Normal.
[0316] Possible clinical uses of this include, for example,
treatment of cardiac arrest, MI, intraoperative organ protection,
head trauma, stroke, and hemorrhagic shock. This arrangement could
be used to cool the brain very deeply while keeping the body core
just above the temperature roughly 33-34 C where complications
begin to appear. A neck wrap cooled by circulating cold fluid could
be applied to deepen cooling. Counter warming--discussed in detail
below--by heated blanket, on the body core or extremities or by
surface warming of the scalp, or face could be applied to balance
the "spillover" cooling--that is the cooling of venous blood due to
the cold zone created in and around the aerodigestive tract.
Warming of the neck surface could also be employed if care is taken
to avoid the areas closest to the carotid arteries
[0317] 4. Rapid Lowering of Core Temperature Especially Near the
Spinal Cord, without Control of Brain Temperature.
[0318] Possible clinical uses can include, for example, treatment
of spinal cord injury, MI, intraoperative organ protection,
fever.
[0319] 5. Rapid Elevation of Core Temperature, without Control of
Brain Temperature.
[0320] Possible clinical uses of this include, for example,
treatment of accidental hypothermia/exposure.
[0321] 6. Controlled Elevation of Brain Temperature, with Control
of Core Temperature.
[0322] Possible clinical uses of this can include, for example,
rewarming after induced hypothermia.
[0323] 7. Controlled Elevation of Brain Temperature, without
Control of Core Temperature.
[0324] Possible clinical uses of this can include, for example,
rewarming after induced hypothermia.
[0325] At least some of the disclosed systems and methods described
herein allow rapid achievement and maintenance of a significantly
lowered brain temperature (e.g., 35.degree. C., 30.degree. C.,
25.degree. C. or 20.degree. C.) while optionally keeping body
temperature in the vicinity of about 32.degree. C.-38.degree. C.
This capability can be useful, for example, when treating cardiac
arrest, stroke, traumatic brain injury, and other such events. This
capability can also useful to provide perioperative neuroprotection
during such procedures as aneurism clipping and coilings, and
coronary artery bypass grafts (CABG). Also, this capability can be
well-suited for addressing fever spikes that are commonly
associated with brain injury with minimal disturbance of the
patient's core temperature. The systems and methods described
herein can also, in at least some examples, (1) reduce intracranial
pressure after brain injury, (2) reduce the risk of pneumonia
commonly associated with cooling therapy, and/or (3) provide a
means of controlled re-warming, whereby the brain is returned to
equilibrium with the body by reducing the brain focused cooling or
using brain focused and/or body focused warming.
[0326] In some examples, a warming function can be provided to
further improve the selectivity of the device. The system can also
include an interface kit that contacts the patient and a base unit
that does not contact the patient or fluids going into or out of
the patient. The base unit can be reusable because it is generally
maintained separate from the patient. In some examples, the systems
and methods discussed herein can also include a single use heat
exchanger that can be interfaced with the re-usable base unit.
[0327] An interface system (or kit) can comprise a fluid path and,
if desired, associated protective equipment. The fluid path can be
configured for a single use. Accordingly, in some examples, the
fluid path is referred to as a single use fluid path. However, it
should be understood that the fluid path can alternatively be
configured to be sterilized for reuse.
[0328] As discussed in more detail below, the interface system can
comprise one or more of the following components: nasal
catheter(s), esophageal catheter(s), tracheal catheter(s), oral
catheter(s), return manifold(s), switching valve(s) or clamp(s),
filter module(s), waste reservoir(s), connecting line(s),
recirculation reservoir(s), vent(s) for reservoir(s), heat
exchanger(s), manifold(s) associated with the heat exchanger(s),
and straps and/or adhesives to secure one or more of the catheters
of the system as desired. As will be understood by one of ordinary
skill in the art, various combinations of these and other features
described herein are possible in connection with providing a novel
interface system in accordance with the disclosed embodiments.
[0329] Associated protective equipment can include, for example,
disposable covers for temperature probes that contact the patient
or disposable temperature probes.
[0330] A single use fluid path can comprise one or more nasal,
esophageal, tracheal, and oral catheters. For example, two single
or multi-lumen nasal catheters can be configured to be introduced
through the nostrils of the patient. The tip of each catheter can
be inserted to a depth of 1 to 15 cm from the nares. The lumens of
the catheters enable fluid communication of the nasopharynx with a
source of fluid, which can be, for example, between -20.degree. C.
and 37.degree. C. Clamps, straps, adhesive, or other means of
affixing the catheters to the patient can be included. These
catheters can include foam or other such flow restricting members
to prevent fluid introduced into the nasopharynx from leaking back
out the nose. In other embodiments, an apparatus can be configured
to enclose the nose. These catheters can also include multiple
ports to direct fluid flow toward key structures in the pharynx
such as the turbinates or the orifices of the sinuses. If desired,
these catheters can be notched, marked or color coded to indicate
depth of insertion. Clamps or valves can also be used to adjust
flow rates in the catheters.
[0331] An esophageal catheter can also be included with the
interface system. The esophageal catheter can comprise a
multi-lumen catheter. The tip of the catheter can be inserted so
that the distal tip lies within the esophagus. A primary lumen
(preferably larger than one or more secondary lumina) can extend
from a proximal end of the catheter to a distal end, providing
access to the stomach and/or a means for emesis to leave the
stomach. A secondary lumen can extend from the proximal end and
terminate inside a flexible balloon located near the distal end.
The balloon can be inflated to reduce or prevent entry of fluid
into the stomach from the esophagus. Another (e.g., a third) lumen
can extend from the proximal end to a port proximal to the balloon
to provide fluidic communication between the port and a source of
fluid (e.g., fluid at a temperature between -20.degree. C. and
37.degree. C.) or a source of negative pressure. This third lumen
can be used to irrigate the esophagus with cold fluid or to remove
fluid from the esophagus proximal to the balloon. Additional lumens
can be provided to facilitate the above or other purposes, such as
to provide an additional balloon, additional fluidic communication
between the proximal portion of the esophagus and the outside of
the body environment, fiber optic devices, and/or pressure
measurement or temperature measurement probes.
[0332] FIGS. 18A-C and 19A-D illustrate various esophageal
catheters that can be used in connection with the cooling and
temperature management systems described herein. FIGS. 18A-C
illustrate various multi-function esophageal catheters; however,
many other embodiments are possible by, for example, added lumens
for access of additional instruments, added irrigation lumens, etc.
One example would be adding lumens to accommodate thermocouples or
optical temperature sensors to measure esophageal temperature above
and below the esophageal balloon. Comparison of the "dry" and "wet"
esophageal temperatures can provide information on cooling rate and
serve as a macroscopic leak detector. Also, similar functionality
can be created, for example, by affixing a bundle of tubes
together, or one or more tubes to the outside of a standard
esophageal catheter. The multi-functional esophageal catheter may
also include grooves, fins, or side (non-annular) balloons for the
purposes of promoting even flow of cooling fluid, or distending the
esophagus in a manner favorable for heat transfer (such as
increasing surface area or reducing distance to key arteries).
Catheters of the present invention can also comprise non-circular
channels (e.g., depending on a desired pressure within the system
(e.g., the catheter or the cuff), a desired flexibility of the
catheter, etc.). Flow in lumens can also be reversed when it is
desired to remove fluid form the patient.
[0333] FIGS. 19A-D illustrate a "double section" balloon esophageal
catheter that can be used in embodiments of the cooling and
temperature management system disclosed herein. A suction lumen can
be positioned between the balloons to create a small zone of low
pressure when suctioned to help prevent fluid migration beyond the
"lower" cuff, which governs entry of fluid to the stomach. An
alternative configuration includes an optional second balloon line,
allowing separate inflation of balloons. This has the added
advantage that the compressed area of the esophagus can be changed
from time to time.
[0334] A tracheal catheter can also be included with the interface
system. The tracheal catheter can comprise a multi-lumen catheter.
The tip of the catheter can inserted so that a distal tip is
positioned within the trachea. A primary (preferably larger) lumen
can extend from a proximal end to a distal end, providing access to
the large airways of the lung for the passage of air, respiratory
gases, medications, and/or instruments. A second lumen can extend
from the proximal end and terminate at (e.g., inside) a flexible
balloon located near the distal end. The balloon can be inflated to
reduce or prevent entry of fluid into the lungs from the trachea
proximal to the balloon (subglottic space). A third lumen can be
provided to extend from the proximal end to one or more ports near
the distal end but proximal to the balloon to provide fluidic
communication between the port(s) and a source of fluid or vacuum.
The third lumen can be used to allow the removal or delivery of
fluid to the subglottic space.
[0335] FIGS. 20A-C illustrate exemplary embodiments of a
multi-lumen tracheal catheter for use with the cooling and
temperature management system disclosed herein. Many other
embodiments are possible, including added lumens for access of
additional instruments, added irrigation lumens, etc. Also, similar
functionality can be created by affixing a bundle of tubes
together, or one or more tubes to the outside of a standard
endotracheal tube. Flow in lumens can also be reversed when it is
desired to remove fluid from the patient. The balloon can be
inflated to shield the lungs from fluid in the trachea.
[0336] FIGS. 21A-D illustrate exemplary embodiments of a "double
section" balloon tracheal catheter that can be used in embodiments
of the cooling and temperature management systems disclosed herein.
A suction lumen is positioned between the balloons to create a
small zone of low pressure when suctioned. This prevents fluid
migration beyond the "lower" cuff governing entry of fluid to the
lower trachea. The balloons can be inflated to shield the lungs
from fluid in the trachea. The shielding effect can be increased by
connecting the lung access lumen to a ventilator and adding a
slight positive pressure to the lungs. This shielding effect is
synergistic with the effect created by low pressure zone between
the balloons. An alternative configuration includes an optional
second balloon line, allowing separate inflation of balloons. This
has the added advantage that the compressed area of the trachea can
be changed from time to time.
[0337] One or more oral catheters can also be included with the
interface system. The oral catheter(s) can be inserted to the back
of the mouth to remove irrigation fluid from the patient and/or
deliver irrigation fluid to the pharynx. The catheter can be in
fluidic communication with a return manifold and/or a delivery
manifold. The fluid in the oral catheter can be moved by pump or
vacuum. In some cases, the oral catheter can be a lumen of the
tracheal tube and/or the esophageal tube, or it can be a dedicated
line that suctions liquid from the mouth area. The suctioned fluid
can be discarded, or filtered and then re-circulated. A key point
is that the flow rate entering the oral catheter can be adjusted
independently of the fluid delivery rate, thus allowing control of
the liquid level in the patient's mouth. For example, the oral
catheter can be manually adjusted to alter the height of the fluid
column within the pharynx. The oral catheter can comprise one or
more ports in the catheter wall that can be used to adjust the
height of the fluid column within the pharynx. The oral catheter
ports can also be encased in a mesh or filter that would prevent
adherence of the catheter to the mucosa when suction is active.
[0338] As noted above a return manifold can be provided in fluidic
communication with the oral catheter to allow fluid in the oral
catheter to be discarded or re-circulated. A switching valve or
clamp can also be provided to allow a user to route fluid leaving
the patient to the recirculation reservoir or the discard
reservoir. The valve can be disposable and interfaced with external
automation. Alternatively, the valve can be manually operable.
[0339] A filter module can also be provided. The filter can be
configured to accept fluid to be re-circulated. The filter removes
bacteria and particles greater than 0.1 micron or greater than 0.5
micron or greater than 1 micron or greater than 5 microns or
greater than 10 microns in size. A series of filters of varied size
can also be utilized.
[0340] A waste reservoir can be provided to receive fluid that is
to be discarded. The waste reservoir can have a capacity between
about 1 and 20 liters. The reservoir can have at least one inlet
and, if desired, can be at or below atmospheric pressure to
facilitate waste removal. Waste reservoirs and recirculation
reservoirs can comprise a sleeve and/or bag configured to hold
fluid and configured to be removed and replaced at the end of the
procedure.
[0341] Additional features can include a line for connecting the
waste reservoir to a vacuum source, and a vent for the waste
reservoir. The vent can be configured so that it can be opened or
closed as desired.
[0342] In some examples, a recirculation reservoir can also be
provided. The recirculation reservoir can receive and hold fluid
for recirculation. If the fluid is to be filtered, the fluid can be
filtered before entering or after leaving the recirculation
reservoir. The recirculation reservoir can also accept an initial
charge of fluid. The recirculation reservoir is at or below
atmospheric pressure. The reservoir can have a capacity of 1-20
liters. In some cases the reservoir can be incorporated into the
heat exchanger, with the "hold up" volume of the heat exchanger
replacing all or part of the reservoir volume. At the start of
cooling, the reservoir can be charged an initial charge of cooling
fluid, which may be, for example, about 2 L of 0.9M saline;
however, other concentrations and formulations of fluid may be used
as disclosed herein. The reservoir can also accept additional fluid
volumes during therapy to compensate for any fluid lost due
intentional discard, leaking, spillage, etc.
[0343] A line can be provided for connecting the recirculation
reservoir to a vacuum source. One or more vents can be associated
with the recirculation reservoir and the vents can be operable
between and open and a closed position, either in a manual or
automated manner.
[0344] The systems of the present invention can comprise one or
more heat exchanger (e.g., plate-type heat exchanges, shell
exchangers, tube exchangers, etc.). In some examples, the heat
exchanger comprises a single use heat exchanger in fluid
communication with the recirculation reservoir. The heat exchanger
can be configured to exchange thermal energy with a reusable
cooling unit. The heat exchanger can, in some examples, be in
thermal contact but not fluidic contact with the cooling unit. In
other embodiments, the heat exchanger can be in fluidic contact
with the cooling unit, but provide two or more distinct fluid
paths. The heat exchanger can be made of relatively high
conductivity materials, such as various metals including, for
example, copper, aluminum, and/or steel. The heat exchanger can, in
some examples, be configured to allow between 100 and 2000 watts of
heat exchange, and can be configured to accommodate flow rates
between, for example, 0.2 and 5 L per minute (e.g., having a
pressure drop of less than 15 PSI). The heat exchanger can be
configured to provide a fluid path with a high surface area of up
to 1 m.sup.2 and interface with the base unit as described in more
detail herein. Of particular interest are cases where fluid path
through the heat exchanger is "very long" such that the temperature
of cooling fluid is nearly completely equilibrated with that of the
exchanger walls. For a rectangular channel geometry, this
equilibration will occur when the dimensionless length of the
channel is greater than about 1.2, with values above 2.0 being
especially desirable (see Middleman, S An Introduction to Heat and
Mass Transfer, p458) Thus the temperature of the cooling fluid
entering the patient is readily inferred from that of the heat
exchanger and/or base unit platens, and thus controlled. The
portions of the heat exchanger that are not in direct physical
contact with the cooling elements of the base unit can be insulated
to reduce heat exchange with ambient air. It is understood that
some condensation occur even on the insulated sides, for this
reason the sides are shaped to direct condensate into a drain or
waste container.
[0345] A manifold in fluidic communication with the heat exchanger
can also be provided. The manifold can divide the flow of cold
fluid, as desired, between the esophageal catheter and the nasal
catheters.
[0346] Various straps and/or adhesives can also be provided to hold
or maintain one or more of the catheters in a desired position.
[0347] In some examples, a tracheal tube can be in place in a
patient prior to implementation of one or more components of the
interface kit. In such cases, in can be desirable to leave the
preexisting tracheal tube in place rather than disrupt the airway.
Thus, it might not be desirable to insert a new or additional
tracheal tube, such as those described herein, until it is safe to
do so. Nevertheless, cooling could still be accomplished without
the tracheal suction.
[0348] An optional warming functionality may also be included. A
warming device can provide warmth to the body core to counteract
the cooling of the core caused by venous blood returning from the
cooled brain through the cooling zone along the aerodigestive
tract. Warming can be provided by hematogeneous and or surface
warming strategies. For example, a warming device can comprise one
or more heated blanket or pads that can be positioned on or around
the patient. Warming of the scalp or face is another possible
strategy.
[0349] Thermal energy can be supplied to one or more warming
devices by recirculating warm fluid, forced warm air, or direct
resistive heating. In some embodiments, where an array of
thermoelectric cooling devices is used, an additional "hot side"
heat exchanger can be provided to remove heat from the hot side or
heat sink of the thermo electric devices. This has the advantage of
improving the efficiency of the thermoelectric device while
avoiding the need for cooling fans. A further advantage is that the
use of this recaptured heat allows for a smaller and potentially
safer heating system.
[0350] One or more temperature probes can be provided to monitor
the temperature of the warming device and/or skin temperature of
the patient. This measurement can be used, for example, to monitor
the warming device to reduce a risk that the warming device gets
the skin too hot (e.g., beyond about 42.degree. C.), thereby
delivering too much heat to the patient and possibly harming the
patient's skin.
[0351] The power supplied to the warming device can be modulated as
a function of the rate of energy removal, measurements of patient
temperature, especially rectal temperature, bladder temperature,
brain temperature, venous blood temperature, and/or the total
energy removed from the patient by the cooling device. The warming
device can be used to maintain the body near normothermic
temperature of 37.degree. C. as measured by rectal or other
temperature probe, while the brain is maintained at a lower
temperature. In this way, the neuroprotective advantages of cooling
the brain can be achieved and the occurrence of complications
associated with cooling the body can be reduced and/or
substantially eliminated.
[0352] The warming device can also be used to maintain the body
near a lowered temperature set point of about 32.degree.
C.-36.degree. C. as measured by rectal, bladder or other
temperature probe, while the brain is maintained at a still lower
temperature. In this way, the neuroprotective advantages of deep
cooling the brain can be achieved and the occurrence of
complications associated with cooling the body can be held at a
controlled, acceptable level.
[0353] If the temperature probes that are used are not disposable
in their entirety, disposable covers can be provided for contact
with the patient and with fluids contacting the patient. In some
examples, the covers are thin conductive plastic and/or rubber.
[0354] A base unit can be provided to interface with the patient
interface system/kit described herein. The base unit can comprise
one or more of the following components: reusable and/or disposable
temperature probe(s), fluid temperature measuring device(s),
processor and/or data acquisition system(s), reusable cooling
unit(s), heat removal device(s), pump(s), pump control unit(s),
and/or cooling unit(s). As will be understood by one of ordinary
skill in the art, various combinations of these and other features
described herein are possible in connection with providing a novel
interface system in accordance with the disclosed embodiments.
[0355] In some examples, the base unit can be configured to enable
the user to measure data from the patient. For example, the base
unit can be configured (e.g., by placement of temperature sensors)
to receive, obtain, and/or display a temperature of the patient at
certain locations (e.g., brain, rectal, tympanic, axillia, skin,
central venous, temporalis muscle, distal to an esophageal and/or
tracheal cuff, proximal to an esophageal and/or tracheal cuff,
external ear, toe, finger, exhaled gas, etc.). Not all possible
measurement locations need be obtained. In some examples, a simple
rectal temperature measurement is sufficient. However, brain
temperature can be critical. For example, in some embodiments, a
temperature sensor can be disposed exterior or interior to entrance
catheters (catheters through which the cooling fluid can enter the
aerodigestive tract) and exit catheters (e.g., catheters through
which cooling fluid can be actively removed from the aerodigestive
tract). These temperature sensors can be coupled to the base unit
and configured such that the base unit can measure a temperature
difference (e.g., to provide a user with at least some information
regarding brain temperature).
[0356] Other temperature monitoring methods and/or devices can be
used to help accurately determine brain temperature. For example,
an invasive method can comprise disposing a bolt in a subject's
brain (e.g., in the event that cranial pressure should be released
and/or an accurate temperature reading should be obtained). As
another example, temperature sensors can be coupled to a line and
inserted intravenously (e.g., in a jugular) and positioned near to
the brain. As yet another example, a non-invasive method can
comprise exposing a subject to an MRI during a procedure to obtain
one or more temperature readings.
[0357] The base unit can also be configured to receive, obtain,
and/or display measurements of pressures in the patient, including,
for example, pressures in the trachea, esophagus, and/or
intracranial areas of the patient. For example, an esophageal
and/or endotracheal cuff can be configured (e.g., with a pressure
sensor) to detect and/or measure a pressure (e.g., a pressure
inside the cuff). A base unit can be coupled to the pressure sensor
(e.g., via an electrical connection running within a catheter) such
that the base unit can receive and/or obtain detections and/or
measurements from the pressure sensor. A base unit can further be
configured such that when a threshold pressure is met or exceeded,
an alert (e.g., audio, visual, etc.) occurs. In some embodiments,
the threshold pressure can be adjusted by a user. The threshold
pressure can also be pre-determined (e.g., based on the anatomical
deployment of the cuff, a cuff material, and the like). In other
embodiments, a pressure within a cuff can be automatically
adjustable based on pressure detections and/or measurements from
the pressure sensor, a desired pressure, anatomical deployment of
the cuff, a rupture pressure, and the like.
[0358] In other embodiments, the base unit can further be
configured to measure flow rate of the cooling liquid. A flow
sensor can be positioned (e.g., within the base unit, along a
length of one or more catheters (e.g., interior or exterior),
within a cuff, and the like) such that the flow rate of the cooling
fluid can be measured going into and out of (e.g., in the case of
active removal of the liquid) the subject.
[0359] Other sensors and/or measurement devices can be configured
to interface with the base unit such that the base unit can receive
information (e.g., an IV unit can send and/or permit the base unit
to obtain information regarding fluids delivered by the IV unit to
a subject).
[0360] In some examples, the base unit can be configured to provide
motive force to move fluid into or out of the patient, add or
remove heat from the fluid entering the patient, and/or display
certain data on the patient's condition (including, for example,
the temperature and/or pressure readings described above). The base
unit can provide a simple closed loop feedback control of a single
temperature, or in more sophisticated embodiments can allow the
user to program certain time courses for patient temperatures, such
as approaching a given temperature set point at a specified rate,
holding the patient near a specified temperature for a specified
period of time, and re-warming the patient at a specified rate.
[0361] The base unit can comprise a re-usable or disposable
temperature probe for use in monitoring patient temperature in
communication with a temperature display. More than one temperature
probe may also be used. In some examples, there can be at least a
measurement of rectal temperature of the patient. Optional
temperature probe(s) can be used to measure temperature of liquid
entering and returning from the patient. In some examples, the
temperature probes can be isolated from the fluid by a disposable
but highly thermally conductive material such as a thin aluminum or
plastic sleeve. In some examples, a thermally conductive grease or
gel can be used to enhance thermal contact between the probe
sending element and the sleeve. A processor and/or data acquisition
system can be provided and configured to communicate with and/or
receive information from the temperature probe or probes. A display
screen or other such device can be provided to display the
information received from the one or more temperature probes.
[0362] A reusable cooling unit can be provided and configured to
accept a heat exchanger. In some examples, the heat exchanger
comprises one or more e cartridge with a rectangular "box"
geometry. The cartridges can be--but are not required to
be--removable and/or disposable. The cartridges can comprise an
inlet and outlet port on the same or different sides of the
cartridge. The cooling unit can be configured to close to bring one
or both sides of the cartridge into thermal contact with the
cooling elements. In this manner, heat can be transferred by
conduction without the cooling elements being in fluidic contact
with the cartridge. The contact with the cartridge can be
established with one or two smooth and/or featured conduction
surfaces constructed of a thermally conductive material such as,
for example, aluminum, steel, or copper. In some examples, the
conduction surfaces can also be in contact with an array of
thermoelectric cooling devices (described in more detail below)
that pump heat away from the surfaces, reducing their
temperature.
[0363] In some examples, one or more devices to remove heat from
the "hot" side of the thermoelectric devices can be provided.
Removal of heat can be by free convection or enhanced by use of
fins, fans, or by attaching a "heat pipe", a heat pipe being a
reservoir of fluid that is warmed or boiled by waste heat from the
thermoelectric devices. The warmed fluid can move via capillary
action, or by gravity. In the gravity driven case, he fluid vapor
can rise to another part of the reservoir in thermal contact with
the ambient environment, and condense there dissipating heat to the
environment. The fluid can then fall back into the reservoir after
condensing. Alternatively, the fluid can be pumped to a cool part
of the reservoir or a cooling coil.
[0364] In some examples, at least one pump can be positioned before
or after the heat exchanger to propel fluid into the patient. The
pumps can be peristaltic pumps to prevent fluid contact with the
pumping mechanism. In some examples, however, diaphragm pumps and
other types of pumps such as a rotary pump can be suitable. If
desired, a disposable fluid contact section can be provided with
the diaphragm or rotary pump.
[0365] The pump(s) can deliver up to 0.2 l/min, between 0.2 and 2
l/min, up to 2 l/min, between 0.5 to 10 l/min, between 10 and 20
L/min or in some examples, up to 20 l/min. Depending on a desired
startup speed, intermittent pump timing and pre-cooled liquid can
be considered. In some examples, two peristaltic pumps can be
provided to propel fluid into the patient, with one pump governing
the flow rate into one or more esophageal catheters and the other
governing flow rate into one or more nasal catheters. A control
unit can be provided to allow the user to control the speed of
pumping and/or to turn the pump(s) on or off.
[0366] One or more cooling units can be provided to interface with
the heat exchanger, a user interface, and/or the data acquisition
system. The cooling unit can use one or more thermoelectric devices
(e.g., to permit modulation of cooling output). In other
embodiments, other types of cooling can also be used, such as an
ice bath or a conventional refrigeration unit. In other
embodiments, recirculating chillers (e.g., thermoelectric or
conventional refrigeration) can be used to permit cooled fluid to
enter one side of a heat exchanger, where another side of the heat
exchanger comprises fluid to be introduced to a patient. The
recirculating chillers can be adjusted to permit modulation of the
cooled fluid. Recirculating chillers can comprise 1000-2000 watts
of cooling capacity at 0.degree. C.
[0367] The data acquisition system can be configured to interface
with the control unit and the temperature probes that come in
contact with the patient. A module associated with the data
acquisition system can be configured to acquire data on the
temperature of the liquid streams entering and returning from the
patient. The module may acquire intracranial pressure data (ICP) in
some cases.
[0368] In some examples, cooling unit can comprise a system with a
dry interface with the heat exchanger. Thus, the heat exchanger can
be in thermal contact with the interface, but not fluidic contact
with the cooling/heating elements of the base unit. In some
examples, the interface can be a two-sided interface that allows
for maximum cooling of the working fluid with minimal residence
time.
[0369] A variety of heat sink strategies can be used to dissipate
heat from the "hot" side of the thermoelectric device as rapidly as
possible. For example, fans can be used to force air over a finned
heat exchanger. Alternatively, and preferably in many cases, the
hot side of the thermoelectric device can be put in contact with a
circulating liquid and the liquid used to simply dump the waste
heat or even to warm the patient. Another possible heat sink
strategy employs one or more reservoirs of liquid with significant
head space being in thermal contact with the hot side of the heat
exchanger. When the thermoelectric devices are cooling the patient,
they are simultaneously boiling the liquid in the reservoirs the
liquid will condense on the interior surfaces of the reservoir,
which will result in the heat being conducted away to the
environment. In some examples, the thermoelectric elements can be
used to warm the fluid going into the patient by, for example,
conducting heat from the environment into the "cold" side of a
thermoelectric device. This arrangement has the advantage of
reduced complexity compared to forced air cooling/warming. The
concept is similar to that of a reflux condenser.
[0370] The term "heat sink" as used herein also includes heat
pipes. Various working fluids can be utilized in such heat pipes,
including, for example, water, ethanol, methanol, fluorocarbons,
and any mixtures of those. The temperature at which the pipe
operates is determined by the pressure inside the reservoir. In one
example, the temperature of heat pipe operation can be between
45.degree. C. and 55.degree. C., which is generally warm to the
touch but not a burn hazard.
[0371] In some examples, the heat pipe can be a gravity heat pipe.
In other examples, the heat pipe can be operable using capillary
action, such as conventionally used in high performance computers.
Heat pipes can provide several advantages over the use of
conventional fan and fin systems to dissipate heat. For example,
fan and fin system can be more difficult to clean. In other
embodiments, as described above, a heat exchanger (e.g., a plate
heat exchanger) can be in fluid communication with a cooling unit
(e.g., configured to cool fluid directly entering a patient or
indirectly through a heat exchanger).
[0372] Management of a given patient's temperature can comprise
three basic phases. An initial cooling or "induction" phase can be
performed to bring the patient to a hypothermic or normothermic
state. This phase can be followed by a "maintenance" phase where
the patient's brain and body temperatures are maintained at their
respective goal temperatures as determined by the physician for a
period of time ranging from a few hours to several days. Finally a
"re-warming" phase can be provided in which the brain and body are
returned to their normal temperatures in a controlled fashion.
[0373] FIG. 11 illustrates an exemplary "long column" cooling
strategy and can be used to describe the resulting fluid flow
field. By providing a longer cooling zone than "nasal only"
strategies, the long column method allows for faster and deeper
cooling. In addition it allows a larger steady state gradient
between brain temperature and body temperature to be achieved and
maintained.
[0374] As shown in FIG. 11, cold fluid can be supplied through
nasal catheter 401 and multi lumen esophageal catheter 402. Fluid
can exits into esophagus through port 403 while fluid loss to the
stomach is prevented with balloon 404. Balloon 404 can also
regulate aspiration of stomach contents. Large lumen catheter 405
can preserve stomach access and prevents pressure increase in the
lower esophagus or stomach by providing an exit path for emesis and
intestinal gas.
[0375] Fluid entry into lower trachea 406 can be reduced or
prevented by balloon 408 and port 409 can permit the removal of
fluid in the trachea to help reduce and/or prevent fluid
stagnation. Fluid entry in to the lower trachea may be further
reduced by using a ventilator to create a slight positive pressure
in the lungs. A main lumen of a multifunctional endotracheal
(tracheal) tube 407 can permit respiration. Main exit line 410 can
be configured to recover fluid for filtering and recirculation or
disposal. Patient may be placed flat or in Trendelenberg position
to aid fluid removal
[0376] In use, the system shown in FIG. 11 (and in other figures as
applicable) can be implemented as described in the exemplary method
below;
1. Induction Phase (Once it is Determined that Cooling is
Appropriate for a Brain Injured Patient)
[0377] a. If not already intubated, a cuffed ETT (with or without
additional ports and lumens) is inserted to protect the lungs. The
ETT may have additional lumens and ports. The cuff is inflated to a
pressure of 20-50 cm water. If a double balloon or cuff ETT or
catheter is used, its second balloon can be inflated.
[0378] b. An esophageal tube is inserted into the esophagus and its
cuff inflated to 20-60 cm water to protect the stomach.
[0379] c. Nasal catheters are inserted into the nostrils.
[0380] d. The oral catheter is placed in the mouth.
[0381] e. The liquid carrying tube lines are attached to their
respective manifolds (nasal, tracheal, esophageal, and return).
[0382] f. The return line is connected to the reservoir.
[0383] g. The fluid path is completed by placing the single use
heat exchanger or heat exchangers in the cooling unit and possibly
the warming unit.
[0384] h. The reservoir is charged with cooling fluid
[0385] i. The cooling unit is activated.
[0386] j. The pumps are activated.
[0387] k. Fluid flow is now established and can move in a circuit
(see, e.g., FIGS. 10A, 10B, and 10C).
[0388] l. The flow field inside the patient (see, e.g., FIG.
11).
[0389] m. Given that the aerodigestive tract may contain infective
material such as gastric contents or pharyngeal fluid, the first
liter or so of fluid exiting the patient may be discarded and not
recirculated. If a double balloon tracheal catheter is used,
flushing or slight suction may be applied to the space between the
balloons or cuffs in the trachea to shield the lungs from infective
fluid ingress. In addition, pressure may be slightly increased in
the lungs using a ventilator to further shield against fluid
ingress into the lungs.
[0390] n. Measurement devices (thermocouples or thermistor based
devices) are introduced in the rectum, or axillia. If a central
venous line and or "bolt" are present these temperatures can be
acquired. Intracranial pressure data may also be acquired if
available.
[0391] o. After the cold fluid circuit is established, brain
temperature will decrease rapidly, while body temperature will
decrease more slowly than that of the brain. During induction, it
is possible that the warming function will not be used.
[0392] p. A patient's body core temperature can be left near normal
temperatures. In other cases, however, a patient can be cooled
until body core temperature is below 36.degree. C., 35.degree. C.,
34.degree. C., 33.degree. C., 32.degree. C., or lower, and in some
cases 26.degree. C., 25.degree. C., 24.degree. C., or lower. It is
desired that the brain will be colder than the core temperature. As
the core temperature approaches its set point, the warming unit
will be engaged, eventually reaching a steady state where the heat
extracted by the cooling unit is balanced by the heat supplied onto
the patient by the warming unit.
[0393] q. In the event that brain temperature measurement is
available and that the brain temperature is the controlled variable
of the control loop, the brain temperature will be monitored and
when the brain temperature approaches its set point, the cooling
will be discontinued and/or the warming unit will be engaged,
eventually reaching a steady state where the heat extracted by the
cooling unit is balanced by the heat supplied onto the patient by
the warming unit.
2. Maintenance Phase
[0394] a. Once the patient reaches goal temperature, control
actions will be taken as needed to maintain the patient in the
vicinity of the goal temperature. Many control methods are
described in the art including PID methods, multi input, single
output control (MISO) and multi-input multi-output control (MIMO).
Internal model control (IMC) can also be used.
[0395] b. In addition to other treatment, intermittent flushing of
the aerodigestive tract may be undertaken to prevent stagnation of
fluids (particularly in the trachea) during this "maintenance
phase."
[0396] c. In addition, intermittent suction may be placed on the
tracheal ports to prevent stagnation of fluids "above" the cuff
protecting the lungs. In this context, "above" means on the side of
the cuff closest to the mouth rather than closest the lungs.
[0397] d. During maintenance phase, both cooling and warming may be
increased to allow a greater gradient between brain and body
temperature. This may correspond with a decrease in the temperature
of the cooling fluid used to irrigate the patient, or an increase
in the duty cycle of the system (e.g., minutes of active irrigation
per hour of elapsed time).
[0398] e. During maintenance phase temperature of the irrigation
fluid may be modulated to increase or decrease the rate of cooling.
The flow rate of the irrigating fluid may also be modified,
including intermittent stoppage of irrigation of all or part of the
aerodigestive tract.
3. Re-Warming Phase
[0399] a. During re-warming, if a warming device is not present,
the cooling system power or duty cycle is decreased and the patient
is allowed to re-warm. If a warming blanket is present additional
energy may be applied to the patient as the cooling is reduced.
[0400] b. As the patient approaches goal temperature, the power to
the warming device is reduced or the warming device is switched
off
[0401] c Fluid is recovered from the patient as needed and
catheters removed when appropriate.
[0402] As discussed above, patients relying on mechanical
ventilation can be particularly susceptible to pneumonia, as
bacteria present in the mouth and pharynx enter the lungs. However,
flushing the upper airway and esophagus with cooling fluid can
mitigate this risk by several mechanisms. First, the flushing
entrains saliva, mucus and pharyngeal fluid, and sweeps the
associated bacteria away. The bacteria are thus prevented from
multiplying and accumulating in the aerodigestive tract. Second the
flushing dilutes the nutrients required by for bacterial growth
reducing the multiplication rate of the bacteria not swept away.
This is especially important in instances where the patient has
recently vomited or in danger of aspirating stomach contents. Third
because the flushing fluid is very cold the temperature of the
surfaces of the aerodigestive tract are reduced considerably,
further depressing the rate of bacteria growth. The net result of
these effects is that any liquid that does enter the lungs is
likely much less infective than that entering the lungs of an
un-flushed patient. It is also possible to add antibacterial agents
and surfactants to the irrigating fluid.
[0403] Patients undergoing cooling for the sake of neuroprotection
are often especially vulnerable to pneumonias because of the immune
system suppression associated with reduction of patient core
temperature. The selective cooling system largely avoids cooling
the core and leaves the patient's own immune system better able to
fight infection. This benefit is further enhanced by the fact that
surface warming can be applied independently, or with an integrated
warming device.
[0404] Flushing can be performed by allowing the fluid to exit and
circulate as described above with respect to FIG. 11 and elsewhere.
In addition, an exemplary method for flushing can be performed as
follows:
[0405] 1. At least the tracheal catheter is introduced into the
patient, but additionally, any or all of the nasal, or esophageal,
catheters as well as the return line are introduced into the
patient.
[0406] 2. The nasal catheter and/or esophageal catheters are used
to introduce fluid in to the patient. Even a lumen of the tracheal
catheter itself may be used.
[0407] 3. Suction is applied intermittently to the suction port of
the tracheal tube.
[0408] The flushing can be part of a cooling process, or it can be
distinct from cooling in that it can be performed with fluid close
to the patient's core temperature.
[0409] FIGS. 22A and 22B illustrate a simplified flushing system in
which fluid is flushed via a multi-function tracheal tube. As shown
in FIGS. 22A and 22B, fluid can be introduced via multi-function
tracheal catheter 501, and enters trachea at port 502. Balloon 503
can restrict and/or prevent fluid entry into the lower trachea,
while a primary lumen (not shown) allows entry and exit of
respiratory gases. Flushing fluid can either overflow into stomach
or can be recovered by application of suction to a lumen that is in
fluid communication with port 502 or to an adjacent lumen in
communication with another port in the vicinity of port 502.
[0410] Temperatures from various sites in, on, and/or near the body
or the device can be used to adjust the function of the device
while in use. These measurements can also be used to estimate
properties that are not directly measured, such as deep tissue
temperature (brain), cardiac output, core heat generation, brain
heat generation and blood flow to the brain. Potential sites of
temperature measurement include, for example, brain, rectum,
esophagus, bladder, tympanic membrane, stomach, pulmonary artery,
vena cava, aorta, exhaled gas, tracheal wall, eye, skin,
peritoneum, axilla, and groin.
[0411] Exemplary cooling systems and related analyses are described
below. A macroscopic heat balance on the patient's body is shown in
Eq. 1 below.
.rho.C.sub.pdt/dt=q.sub.met+q.sub.env+q.sub.cooler+q.sub.warmer
(1)
The left hand side of the equation shows the total rate of change
in heat content of the patient's body as the product of density,
.rho.(x,y,z) heat capacity C.sub.p(x,y,z) and time derivative of
temperature T(x,y,z) represented by their spatial averages averaged
over the entire body. The body's heat content changes in time as a
result of multiple heat flows (measured in joules per unit time,
i.e., watts). The first term on the right side of Eq. 1 is heat
generated by the body itself, q.sub.met, in ordinary situations,
which is balanced by heat exchange with the body's environment,
represented by the second term, q.sub.env at an equilibrium
temperature of about 37.degree. C. When a brain injured patient is
cooled, additional heat is extracted by the cooling device, this
heat flow, represented by q.sub.cooler will cause the patient's
overall average temperature to decrease until a new equilibrium is
established, with metabolic heating being balanced by environmental
and device driven cooling.
[0412] The addition of thermal energy by use of a warming device
such as a such as a heated blanket, contact pads or wrap, can
roughly counterbalance the energy extracted by the cooling device
and lessen this overall decrease in patient temperature. The energy
added by the warming equipment, q.sub.warmer will often be roughly
equal in general (but not always exactly equal) to the cooling
energy, q.sub.cooler. In some cases, however the two energy flows
will be very different, such as during induction of therapeutic
hypothermia when a rapid reduction of patient brain temperature is
required.
[0413] An advantage of this system is that, in some examples, it
can permit care providers to selectively drive the brain to one
temperature while driving the body to another temperature. This can
be helpful because often the optimal therapeutic temperature for
the brain is different than the optimal temperature for the body.
For example, this can be the case when a brain injury results from
cardiac arrest. This advantage can be highlighted by envisioning
the head and body as two separate, but interacting systems as shown
in FIGS. 9A and 9B.
[0414] FIG. 9A is a block diagram showing the major heat flows
impacting the temperature of the brain and body core. The structure
shown in FIG. 9A provides simultaneous brain cooling and body
warming. FIG. 9B is a more detailed block diagram of the major heat
flows impacting the temperature of the brain and body core. In this
representation a third "head" compartment is added to emphasize
that the cooling due to the arterial blood is not perfectly
selective for the brain. However, the flows in the internal carotid
and vertebral arteries do primarily influence brain temperature and
other flows are influencing the brain indirectly after cooling the
body.
[0415] In this model the "head" is considered separated from the
body by a planar control surface at the end of the neck. There is
of course a significant conductive heat exchange between the nasal
cavity and the brain compartment. For this analysis it is lumped
with the hematogenous cooling and treated as part of"q a cooler"
and is not shown separately for the sake of brevity.
[0416] The heat balance on the head is given in Eq. 2, where
quantities denoted with a superscript `h` are total fluxes to and
from the head. While recognizing that the temperature profile of
the head is heterogeneous, this makes the point that the average
temperature of the head can be manipulated by changing the energy
content of the blood leaving the body core, q.sub.artery, as is
done with systemic cooling devices. However, in this case the blood
energy flow is largely controlled by q.sup.a.sub.cooler, which the
heat extracted from the artery by irrigation of the aerodigestive
tract with cold fluid from the cooling unit. The temperature of the
brain in turn affects the temperature of the exiting venous blood
and thus the energy flux leaving the brain area toward the body,
q.sub.vein
.rho. h C p h _ T h _ t = q artery + q cooler a + q met h + q env h
- q vein ( 2 ) ##EQU00001##
The heat balance on the body core is given in equation 3 where
quantities denoted with a superscript `c` are totaled fluxes into
the body core. While recognizing that the temperature profile of
the body core is heterogeneous, the average temperature of the body
core is impacted by the energy flow of the venous blood leaving the
head, q.sub.vein which is in turn influenced by heat extracted from
the veins due to proximity with the aerodigestive tract,
q.sup.v.sub.cooler. The average temperature of the body core can
also be manipulated through the use of an external warming device,
and this heat flux, q.sup.c.sub.warmer can provide a counter
balance to the energy required to warm the returning cold venous
blood.
.rho. c C p c _ T c _ t = - q artery + q met c + q env c + q vein +
q cooler v + q warmer c ( 3 ) ##EQU00002##
summing the metabolic heat generation of the body core and the head
yields the total heat generation of the body
q.sub.met.sup.h+q.sub.met.sup.c=q.sub.met (4)
By the same logic,
q.sub.env.sup.h+q.sub.env.sup.c=q.sub.env (5)
And
q.sub.cooler.sup.a+q.sub.cooler.sup.v.apprxeq.q.sub.cooler (6)
And finally, again using the same logic to describe the heat
content of the entire body gives Eq. 7.
.rho. h C p h _ T h _ t + .rho. c C p c _ T c _ t = .rho. C p _ T _
t ( 7 ) ##EQU00003##
With these definitions in place adding Eq. 2 and Eq. 3 together
recovers the original energy balance in Eq. 1. And shows how a
stead state heat balance may be achieved Returning to Eq. 2, the
heat balance on the head is re-arranged to group the terms
describing the blood flow leaving the head and body core:
m h C h _ T h _ t = ( q artery - q vein ) + q cool h + q met h + q
env h ( 8 ) m c C c _ T c _ t = ( q vein - q artery ) + q cool c +
q met c + q env c + q warmer c ( 9 ) ##EQU00004##
Solve for body equation for expression in parenthesis and
substitute into brain equation
( q artery - q vein ) = [ - m c C c _ T c _ t + q cool c + q met c
+ q env c + q warmer c ] ( 10 ) ##EQU00005##
This makes combined expression relating change in head temperature
to the change in body temperature. Note that the mass of the head
is much less than that of the body, meaning that the change in head
temperature will be much larger than the change in body temperature
for a given amount of energy delivered
m h C h _ T h _ t = [ - m c C c _ T c _ t + q cool c + q met c + q
env c + q w c ] + q cool h + q met h + q env h ( 11 )
##EQU00006##
[0417] In general the metabolic and environmental fluxes will be
variable so these will be understood as unpredictable "load"
variables. However, the cooler and warmer related fluxes can be
readily manipulated by the user via an automated control
system.
[0418] This analysis shows that the temperature of the brain and
body can be manipulated independently, where q.sub.cooler is used
to control the temperature of blood entering the head, and
q.sub.warmer is essentially used to compensate for the resulting
reduction in the temperature (and thus energy content) of the
returning blood and thus decrease the resulting reduction in the
patients core temperature. The inventors recognize that the model
presented here is simplified in that conduction through the control
surface was neglected, however it could be added in without
significant change in the result, namely that cooling the
aerodigestive tract affects brain temperature to a greater degree
than systemic cooling strategies, and that the resulting
disturbance on body temperature can be countered by systemic
warming, and that the patient can be maintained in thermal
equilibrium with the environment.
[0419] FIGS. 9A and 9B depict relevant heat fluxes, with the
parameters in the above equations and FIGS. 9A and 9B described
below in Table 7.
TABLE-US-00007 TABLE 7 (Summary of variables in heat balance FIGS.
9A and 9B, and Eqs. 1-11) Variable Explanation Note .rho. density
C.sub.p Heat capacity d T _ dt ##EQU00007## Change in temperature
in time d T h _ dt ##EQU00008## Change in head temperature in time
d T c _ dt ##EQU00009## Change in body temperature in time d T b _
dt ##EQU00010## Change in brain temperature in time T.sup.h
Temperature of the head, Temperature profile is including the brain
function of x, y, z position and t T.sup.c Temperature of the body
Temperature profile is core function of x, y, z position and t
T.sup.b Temperature of the brain Temperature profile is (excludes
rest of head) function of x, y, z position and t T.sup.hs Head
compartment surface Influences rate of head temperature heat
exchange with the environment T.sup.cs Core compartment surface
Influences rate of core temperature heat exchange with the
environment q.sub.artery The heat flux transferred Reflects a flow-
from the body core by weighted average of the arterial blood flow
heterogenous body temperature profile q.sub.vein The heat flux
transferred Reflects a flow weighted from the head by returning
average of the venous blood flow heterogenous head temperature
profile q.sub.cooler.sup.a The heat flux removed The arterial heat
flux from the arterial blood arriving in the head is flow by the
cold q.sub.artery + q.sub.cooler.sup.a perivascular tissue
q.sub.cooler.sup.v The heat flux removed The venous heat flux from
the venous blood returning to the body flow by the cold core is
q.sub.vein + q.sub.cooler.sup.v perivascular tissue q.sub.met.sup.b
Heat generated by metabolism within the brain q.sub.met.sup.h Heat
produced in the head by metabolism q.sub.env.sup.h Heat exchanged
between the head and the environment q.sub.met.sup.c Heat produced
in the core by metabolism q.sub.env.sup.c Heat exchanged between
the core and the environment q.sub.warmer.sup.c Heat supplied to
the body by the warmer q.sub.warmer.sup.h Heat supplied to the head
Heat designed to by warming counterbalance cold blood arriving in
the external carotid arteries. q.sub.sink Heat removed from the In
the case a warm side of the cooling thermoelectric cooler is device
used this includes heat generated by the device as well as heat
pumped from the cold side of the device q.sub.loss.sup.c Heat that
the warming In some examples, this device loses to the can be a
significant environment rather than amount of heat relative
supplying to the patient to that actually delivered to the patient
q.sub.loss.sup.h Heat that the head warming In some examples, this
device loses to the can be a significant environment rather than
amount of heat relative supplying to the patient to that actually
delivered to the patient
[0420] FIGS. 10A and 10B illustrate exemplary fluid (liquid, gas,
and mixed) flow in the system. The esophageal and nasal catheters
are supplied with cold fluid in the manner shown. The fluid is
pulled from the reservoir by the pumps and cooled by the heat
exchanger in thermal contact with the cooling unit. Fluid is
removed from the patient by vacuum, but could also be pumped away.
Fluid flow could also be reversed to empty the patient's
aerodigestive tract at any time.
[0421] Further variants could feature the elimination of the
separate oral return line by using a lumen of either or both of the
tracheal and esophageal catheters, or extending one of the nasal
catheters to the oropharynx and employing it as a return line. In
such a case, the other nasal catheter can still be used for
irrigation of the nasal cavity.
[0422] In use, an initial fluid charge can be supplied to the
reservoir the reservoir has a volume of about 2-20 L and is kept
under a vacuum typical of that used in hospitals. The vacuum can be
generated by a vacuum pump included in the unit, or by attaching to
an externally supplied vacuum, such as the house vacuum line. The
fluid can be drawn from the reservoir through the disposable heat
exchanger by the nasal pump and the esophageal pump. The pumps can
be peristaltic pumps and can be configured to move fluid toward the
nasal area and esophagus respectively. Because the lines can be
cold as a result of the fluid inside, the lines that are outside
the patient can be insulated to reduce condensation if desired.
[0423] In the example shown in FIG. 10A, flow from the nasal pumps
is split (e.g., generally evenly) by a manifold and supplied to two
catheters that are each inserted through one of the patients
nostrils. This fluid irrigates the nasal cavity. In other examples,
however, the irrigating fluid can be delivered by only one of the
nasal catheters and the other catheter can be routed, for example,
to vacuum and used as a return line. The esophageal pump shown in
FIG. 10A is configured to move fluid into the body via a lumen of
the multifunctional esophageal catheter. It should be noted that
the fluid in the patient is roughly at atmospheric pressure because
the patient's mouth and possibly nasal cavities are open to the
atmosphere. Thus, this cooling system enjoys a substantial safety
advantage over intravascular systems where the cooling fluid is at
very high pressure. Because the fluid in the patient is very near
atmospheric pressure, the vacuum of the reservoir or the waste
line/container is sufficient to remove the fluid from the
patient.
[0424] In this example embodiment, fluid introduced into the
patient can be recovered primarily by the oral return line. As
shown in FIG. 10A, the oral return line can include a switching
valve that can be manually actuated in some embodiments and
automatically actuated in others. The switching valve can be, for
example, a three way valve, a disposable stopcock or ball valve, or
a pair of pinch valves. In one example, the valve or valves is/are
disposable.
[0425] If the fluid is not discarded, it can be filtered by a
filter or series of filters (a filter module) before returning to
the reservoir for recirculation. Additional fluid may be added to
the reservoir at any time to replace losses due to spills, discard,
etc. Fluid can be recovered from the patient by suctioning through
the multifunctional tracheal catheter. This fluid may be
re-circulated or it can be routed to waste.
[0426] Fluid can also be recovered from the patient by reversing
either or both of the esophageal or nasal pumps by connecting the
esophageal and nasal tubes to vacuum line
[0427] Fluid can be circulated through this system as needed to
modulate patient temperature. The system can be stopped when
cooling is not needed. In general, a flow rate and temperature are
selected for the irrigating fluid, and the amount of cooling is
determined by the fraction of time the pumps are on or off (i.e.,
the duty cycle). However, other modulation of flow rate and/or
temperature can be used to control the amount of cooling provided
to the patient.
[0428] Care is desirably taken to avoid suctioning trauma to the
patient's tissues, and suction lumens typically have multiple holes
in line (like a whistle catheter) or even distributed at different
points around the multifunctional catheter's circumference so that
they are not all blocked simultaneously. For more even circulation,
multiple holes or lumens may be added to the esophageal or nasal
catheters.
[0429] As described above, FIG. 11 shows a flow field of fluid
inside the patient during use. The temperature modulating fluid is
supplied through nasal catheter 401 and multi lumen esophageal
catheter 402. Esophageal fluid exits into esophagus through port
403 while the stomach is protected with balloon 404. Balloon 404
also prevents aspiration of stomach contents. Large lumen catheter
405 preserves stomach access, and provides exit path for emesis.
Distal trachea 406 is protected by balloon 408 and port 409 allows
removal of fluid, preventing stagnation. The oral catheter
functions as a main exit line 410 and recovers fluid for filtering
and recirculation or disposal. Suction through tracheal suction
port 409 (note 409 may actually be multiple ports) is used to
withdraw fluid from the trachea when desired. This has the
beneficial effect of flushing the trachea and reducing potential
for bacterial growth by reducing the "residence time" of fluid
above the cuff protecting the lungs. Alternatively, if flushing
without cooling is desired, the fluid can be made normothermic by
reversing the polarity on the thermoelectric device(s), causing
them to function as warmers rather than coolers.
[0430] FIG. 12 illustrates an exemplary control system that can be
used to allow automated maintenance of desired set points for the
patient's body core, as inferred from measured rectal or other
temperature measurements, and/or brain, as inferred from direct
measurement via trans-cranial bolt, or by a model informed by one
or more measurements that do not invade the brain. The control
system can also enable cooling of the patient to a given set point
with minimal "overcooling" and enable controlled re-warming. This
can be accomplished with PID control with parameters obtained
empirically, by measurement of the patient, or by mathematical
model.
[0431] The control system can comprise one or more of the
following: a temperature measurement probe, a means of transmission
for temperature data to the control unit, a means accepting user
input, a control unit, and a means of transmitting the control unit
output to a final control element (e.g., actuator).
[0432] In one example, a simple on-off feedback control scheme is
provided to cool the brain while keeping the patient's core
temperature above a certain minimum (e.g., a lower control limit,
LCL). The measured and controlled variable can be, for example, a
patient's rectal temperature. The cooling unit can be set by the
user to provide fluid of a programmed temperature in the vicinity
-20.degree. C. to 37.degree. C. The pumps can be set by the user to
provide a flow rate between, e.g., 0.2 and 10 l/min when active.
Once these parameters are fixed, patient temperature can be
modulated by manipulation of the flow rate (on/off) of irrigation
of all or part of the aerodigestive tract. A second control loop
may be used to control the action of the thermoelectric cooling
device(s), such that irrigation fluid is provided at the flow rate
and temperature desired. The power to the cooler (e.g.,
thermoelectric or other) can be modulated to keep the irrigation
fluid cold, but not freezing for example about 2-4 C. This second
control loop can be a traditional PID controller. The desired set
point for the irrigation fluid can be between -20.degree. C. to
37.degree. C. depending on the fluid used and the particular
situation, but the fluid temperature set point is generally chosen
at the start of therapy and kept under control, as opposed to being
manipulated to control patient temperature. This approach minimizes
the duty cycle on the pumps and minimizes the amount of time that
the patient's aerodigestive tract is irrigated. When the patient
core temperature reaches the lower control limit LCL, the pumps are
switched off and kept off until the patients temperature rises
above the upper control limit, or UCL, and cooling is resumed. In
some cases it will be desirable to reverse the pumps and remove any
recoverable fluid from the patient's aerodigestive tract at the end
of the cooling action.
[0433] In another example, a control scheme can employs a PID
controller for the patient temperature as well. This system can be
configured to keep the patient's core temperature within the
vicinity of a user programmed set point. The set point may be
changed by the user (i.e., care provider) at any time. The user can
also change the set point in a gradual fashion (a ramp rate), which
can be useful to control the speed of cooling or re-warming.
Patient temperature can be modulated by manipulation of the flow
rate (on/off) of irrigation of all or part of the aerodigestive
tract, and the patient's own metabolism provides a counterbalancing
warming force. The irrigation time required of the pump(s) can be
calculated by the PID control. The block diagram of FIG. 12
illustrates an exemplary method of implementing this system.
[0434] FIG. 12 illustrates interactions between components to
enable feedback control. A user can interact with a user interface,
with the user commanding set point and ramp rate temperature for
the patient (shown as T.sub.set point). The user can designate a
temperature for the irrigation fluid, which is compared against the
measured temperature of the fluid leaving the heat exchanger,
T.sub.fluid. Measurements may be taken at several points along the
heat exchanger to provide more information about the temperature
profile across the heat exchanger. The cooler controller
manipulates power to the cooling system, represented by I,V
(current and voltage) and, working as a feedback controller,
maintains the temperature of the fluid leaving the cooling system
at the desired temperature. The patient controller then works to
drive the patient temperature, T.sub.measured, to the desired
temperature at the desired rate by turning the irrigation pumps on
and off when indicated by the difference between patient
temperature and set point, represented by the error signal, E.
[0435] The signals to the pumps V1 and V2 can be varied if
different pump speeds are desired. Or, V1 and V2 may be simple
"on/off" signals. The switching valve can be used to discard the
fluid leaving the patient or recirculate it. It is expected that
the pumps will be switched on not only to cool the patient
initially, but to maintain the patient at the desired temperature
in spite of environmental and metabolic heat generation, which acts
as a disturbance or load on the patient (shown as qd). Note TM and
FM are optional temperature and flow measurement devices
respectively. A variety of temperature and flow measuring devices
may be used, but if the heat exchanger is of sufficient
dimensionless length--described earlier, the temperature of the
fluid entering the patient may be readily inferred. Consideration
of the power supplied by the thermoelectric unit and warming unit
(if used) can be used as the basis of an estimate of energy flux
to/from the patient
[0436] Simultaneous cooling and counter warming can provide
significant advantages. To illustrate these advantages, the flow
field in the aerodigestive tract can be characterized and the
resulting rates of heat transfer into the cold fluid can be
estimated. First, the flow can be characterized as laminar or
turbulent. Putting in the physical properties for water gives a
Reynolds number of about 200 this flow is laminar. Taking a Prandtl
number of 13 for water allows calculation of a Nusslet number of
about 15 which implies a convective heat transfer coefficient of
about 440 w/m2K for the "plate." Assuming a more cylindrical
geometry yields a slightly different answer a Re of about 350, and
a Nusslet number of about 15, leading to a convective heat transfer
coefficient of about 300 W/m2 k. Taking a mid-range value between
the two cases gives a convective h of 400 W/m2 k. This convective
transfer is in series with the heat transfer resistance of the
perivascular tissue that separates the airway from the arteries of
interest. Assuming an average distance of about 1.5 cm of tissue in
this area gives an overall heat transfer coefficient of about 35
w/m2K by:
Q = 1 1 h + l k A .DELTA. T . ##EQU00011##
[0437] For reference, if the heat transfer through the tissue side
were infinitely fast, heat transfer would be about 10.times.
faster. Accordingly, since the heat transfer resistance through the
tissue is much larger than the resistance within the fluid filled
airway, maximizing the surface area used for heat exchange, A, in
the above expression as well as the temperature gradient, .DELTA.T
provide greater effects than maximizing flow rate of cooling fluid
once a certain minimum flow rate is reached about 1 to 10 l/min.
Also, decreasing the length scale, I, over which conductive rather
than convective heat transfer takes place can be significant. With
this in mind, devices that use a balloon with re-circulating cold
fluid, such as US 2009/0177258 and U.S. Pat. No. 7,189,253 can be
disadvantageous because the cooling fluid is constrained by the
balloon and cannot make the same intimate contact with the
irregularly shaped features of the pharynx or esophagus as is
possible with a free flowing fluid approach, as disclosed herein.
This decreases both A, the area available for heat exchange and
critically increases I by adding the thermal resistance of the
balloon, and creating "dead spots" where convection cannot sweep
away the thermal boundary layer. Air in these "dead spots" can
further retard heat exchange due to air's low thermal
conductivity.
[0438] A similar analysis can be made for the esophagus with the
flow considered to be laminar in most cases. Again, tissue side
resistance is greater than the heat transfer resistance on the
fluid side. Given the close proximity of the esophagus and lower
pharynx to the carotid, exploiting the esophagus and the
nasopharynx together increases the surface area and column length
available for heat exchange in the region of the body that the
vertebral and carotid arteries traverse.
[0439] An additional point of differentiation versus nasal focused
cooling strategies is apparent when the heat exchange between the
perivascular tissue and the arteries is examined, with the carotid
and vertebral arteries being of particular interest. Assuming a
roughly circular cross section for the artery and a radius of about
4 mm, a Reynolds number of about 400 is computed. Using a Prandtl
number of about 20 to represent blood, a Nusslet number of about 10
can be computed with the following analysis:
Nu _ ( L ) = 1.614 ( L D PrRe ) - 1 / 3 . ##EQU00012##
[0440] It is then possible to determine the extent to which the
warm blood entering the carotid at the aortic arch will equilibrate
with the cold tissue surrounding it by the time it reaches the
circle of Willis in the brain. The expression for the degree of
equilibration can be presented as:
T _ artery - T r T i - T r = - 4 NuZ Re * PrD . ##EQU00013##
[0441] Using the representative numbers above in the expression
reveals that the arterial blood is incompletely equilibrated even
after 20 cm of travel in the carotid artery. This result shows that
maximizing the length of the "cold zone" of perivascular tissue can
be significant, and that exploiting the esophagus in tandem with
the nasopharynx allows the blood to be cooled more thoroughly than
is possible with "nasal only" strategies that cool the upper
pharynx alone and therefore a shorter segment of the carotid and
vertebral arteries.
[0442] FIGS. 13 and 14 illustrate methods of combining cooling of
the brain with warming of the core. Frequently, it will be desired
to warm all or part of the patient's body to counteract the effects
on the body core of cold venous blood returning from the cooled
brain or blood cooled by heat exchange with the aerodigestive tract
while passing through the jugular vein. This counter warming can be
applied to maintain a balance on the heat flows coming into and out
of the patient. Counter warming additionally permits a greater
brain to body core temperature gradient. Such an effect can operate
to reduce the metabolism of the brain temperature, leading to
reduced heat production by the brain.
[0443] The present disclosure includes various counter warming
methods and devices. For example, in some embodiments, the system
can be configured to comprise palm and/or sole counter warming
devices for the hands and feet, respectively. Palms and soles
participate actively in heat exchange. Such palm and/or sole
counter warming devices can be used in addition to or independently
from other warming devices (e.g., hot air blankets, water blankets,
etc.). Palm and/or sole counter warming devices can have numerous
benefits, including, for example, permitting maximum access to a
patient during a cooling procedures (e.g., when a hot air blanket
is not used with the palm and/or sole counter warming devices).
Further beneficial effects can include vasodilation of the palms
and/or soles upon warming the posterior neck, which can lead to
additional core warming.
[0444] In other embodiments, the devices and methods can comprise a
water blanket configured to warm the patient (e.g., an insulated
water blanket). A water blanket can be used in tandem with or
independently from other warming devices (e.g., palm and/or sole
warming devices). In addition to their warming abilities, water
blankets can further assist in gathering data for the system, such
as by measuring fluid temperature into and out of the blanket to
gauge a subject's core temperature (e.g., or at least the
temperature of those portions of the subject in contact with the
water blanket) or by using resistive heating of a defined power and
temperature. Other blankets to assist in maintaining and/or
increasing the body core temperature of a subject during a brain
cooling procedure are, for example, foil blankets (e.g., space
blankets). Furthermore, forced air devices can also be used (e.g.,
"Bair Hugger" Therapy blankets, etc.).
[0445] Other embodiments can include warming devices configured for
other areas of the body. For example, some counter warming devices
include passing warmed air into the lungs (e.g., through a tracheal
tube discussed above). Further, venous warming devices can be used
(e.g., jugular bulbs) to warm veins (e.g., depending on a given
procedure, a given point in the procedure, a desired brain to body
core gradient, etc.).
[0446] Counter warming methods can be performed using one or more
of the counter warming devices and systems discussed in this
disclosure. A warming device, a combination of warming devices,
and/or the warming location can be varied during a procedure,
depending on a core temperature measurement, a given procedure, a
given point in a procedure, a desired brain to body core
temperature gradient, and the like.
[0447] At the end of a cooling cycle, a patient can be re-warmed in
a controlled fashion. As an example, warming can be adjusted to
maintain a patient's body core temperature above a desired level
(e.g., 33.degree. C. to 40.degree. C.). A patient can be warmed at
any desired rate. For example, a user can decrease cooling fluid
(e.g., form 100% to 0%) over a period of time (e.g., 12 hours), and
counter warming can be adjusted during this time period as
well.
[0448] These "steady state gradient" methods can provide additional
advantages. For example, neuroprotection can be achieved by the
cooling of the brain while complications related to body cooling
can be reduced and/or avoided by taking into consideration the
overall heat balance on the patient and returning heat to the
patient's core. This gradient may be maintained for as long as it
is therapeutically beneficial. The exploitation of the pharynx and
esophagus is to create a long cooling zone around the arteries
enables a large gradient between the brain and the body to a degree
not possible with other approaches.
[0449] To create the gradient between brain temperature and body
temperature, the aerodigestive tract can be cooled by irrigation,
while the body is warmed with external warming devices, such as a
warming helmet, pads or warming blanket on the body core or
extremities. Heat lamps or warmed IV fluids could also be used. The
warming devices should not cause the skin to reach temperatures of
more than about 42.degree. C. to reduce a risk of burning the
patient. In one example, warming devices can be configured to
provide a very mild temperature gradient (about 2-7.degree. C.
above the body core) over a large surface area of the patient.
[0450] If a stable difference between brain and body temperature is
desired, a steady state can be achieved by adjusting the duty cycle
of the warming devices to compensate for the heat removed by the
irrigation of the aerodigestive tract, while maintaining the
temperature of the warming devices strictly below the temperature
range likely to cause skin damage (approximately 42.degree.
C.).
[0451] FIG. 13 shows an exemplary arrangement for accomplishing
this aim, where measurements of flow rates and temperatures of
fluids entering the patient are compared with the flow rate and
temperature of fluid leaving the patient to infer the total amount
of heat being extracted by the system. This measurement can be used
alone or in combination with a measurement of power delivered to
the cooling device. FIG. 13 is a representative block diagram of
the patient temperature control system when an integrated warming
device is used. In this embodiment, energy sent to the warming
device can be modulated based on heat removed from the patient but
the control can also be informed by rate of temperature change,
patient size or weight, or mathematical models. The warming heat
can cancel much of the cooling of the body core by warming cold
venous blood returning to the heart. The warming system has in
internal warming controller that can be set to about 40-42.degree.
C. but not higher to avoid damage to the skin. Although only one
warming device is shown in FIG. 13, more than one warming device
can be used if desired. The amount of warming can be modulated by
adjusting the "duty cycle" (e.g., by adjusting the amount of
warming per hour with a simple on/off signal or variable
voltage).
[0452] FIG. 14 shows another exemplary integrated control strategy.
FIG. 14 is a representative block diagram of an embodiment where
energy sent to the warming device can be modulated based on heat
removed from the patient as well as the patient's core temperature.
The control scheme can include other factors as well, including,
for example, power to the cooling unit, rate of patient temperature
change, patient size or weight or mathematical models.
[0453] In this configuration shown in FIG. 14, the temperature and
flow rate measurements on incoming and outgoing fluids are
optional. Irrigation is started to provide a base "cooling load"
and rectal temperature is monitored. When the rectal temperature
goes below a given threshold, the warming devices can be energized
and rise to a target "skin temperature" of a few degrees (e.g.,
2-7.degree. C.) above the desired patient core temperature. The
warming devices can be controlled by PID controllers to hold a safe
set point skin temperature, and then turned on/off as needed to
maintain the patient core temperature in the desired range or into
the vicinity of the desired set point. In this manner the body core
can be held in a substantially normothermic state, while the brain
can be continuously perfused with cooled blood. The cold blood
branching off into the external carotid can optionally be re-warmed
directly with the warming helmet, while the cold blood returning in
the jugular vein can be counteracted with systemic warming measures
such as a warming blanket, to warm any or all of the face, scalp,
neck posterior or warmed gasses that are directed into the lungs
via a ventilator.
[0454] PID control loops of the body core temperature can be
envisioned where the irrigation time (duty cycle) of the cooling
pumps and the active warming time (duty cycle) of the warming
blanket are the parameters modulated to keep the core body
temperature close to the desired steady state set point. The same
control system could warm or cool the body core at a given ramp
rate by making several small step wise changes to the core
temperature set point.
[0455] This system could also be used in a "maximum gradient" mode.
Such a method for establishing and maintaining a maximal gradient
between brain and body core temperature can include one or more of
the following steps: [0456] 1. Commencing cooling of the patient's
aerodigestive tract with an apparatus as described herein.
Exploiting the entire aerodigestive tract can be particularly
useful when paired with systemic warming as the blood leaves the
aortic arch at a temperature representative of the body core. Thus,
the ultimate depth of brain cooling can be largely determined by
the amount of heat that can be extracted from the blood on its
journey from the aortic arch to the circle of Willis. If the length
of the "cold zone" is not maximized--such as in a "nasal only"
cooling strategy--the residence time of the blood in the cooling
zone will be reduced, and the brain will be chilled less deeply
before the blood returns to the body core and is re-warmed. [0457]
2. Controlling the temperature of the irrigating fluid to the
lowest temperature that does not damage the aerodigestive tract
(e.g., between about -20.degree. C. and 20.degree. C.). [0458] 3.
Continuously or nearly continuously providing a flow rate of liquid
to the aerodigestive tract sufficient that the overall rate of heat
transfer is relatively insensitive to variations in flow rate.
Providing flow sufficient such that the controlling resistance to
heat transfer is not convective exchange between the patient and
the irrigating fluid (e.g., about 0.2-10 l/min). [0459] 4.
Controlling the temperature of the surface warming devices to not
exceed about 40-42.degree. C. [0460] 5. Applying the warming
devices to the patient to warm the surface (skin) of the patient.
The warming device can comprise, for example, one or more of a
warming blanket, warming helmet, warming of the face or neck
posteriors(a maximum surface area is preferred when a maximum
gradient between brain and body is desired). [0461] 6. Controlling
patient core temperature by activating the warming system
frequently enough that the patient's core temperature as determined
by rectal and or other measurements is roughly maintained
normothermic (e.g., around 37.degree. C., or for deepest brain
cooling, at least above the temperatures at which complications
arising from systemic cooling begin to appear (e.g., about
32.degree. C.). [0462] 7. Maximizing the duty cycle of the cooling
pumps by, for example, maintaining continuous or nearly continuous
irrigation of the aerodigestive tract with cold fluid.
[0463] Reducing the duty cycle of the pumps (irrigation time per
day for example) would reduce the depth of brain cooling and thus
the amount of counter warming needed. In this way, a steady state
gradient can be set to any arbitrary value between the maximum case
and an un-cooled one.
[0464] Other control systems can be provided. The warming function
will often lag the cooling function, as the body core temperature
takes some time to respond to the irrigation of the aerodigestive
tract. The warming can include, for example, an element of feed
forward control where the warming function is activated based on
heat removed, and thus warming the body core before the patients
core temperature drops appreciably. The start of warming could be
based on the heat extracted from the patient as determined from
measurements of incoming and outgoing irrigation fluid temperature.
This quantity could be used independently or in combination with
temperature measurement data to determine the correct control
actions in the manner shown in FIG. 13.
[0465] This system could also be used in a "maximum selectivity"
mode, where the ratio of brain cooling to systemic cooling is
maximized. The term "maximized" as used herein, refers to an
increase in a ratio to a point that is at or near a maximum. The
term should be understood to include ratios whereby systemic
cooling is less than an actual maximum ratio. This method can be
used to establish and maintain a significant gradient between brain
and body core temperature with minimal power expenditure. Such a
method can also be used if limited cooling power or cooling fluid
is available (such as in a field hospital) or if access to the
esophagus is difficult or otherwise restricted. The method can also
reduce the need for counter warming. In one embodiment, the method
can include one or more of the following steps: [0466] 1.
Commencing cooling of the patient's upper airway with an apparatus
as described herein in other embodiments. The esophageal tube is
not used, and the esophagus is not actively exploited for cooling.
A laryngeal mask, extended oral catheter, or Trendelenberg posture
can be used to reduce fluid entry into the esophagus. Because the
length of the "cold zone" is not maximized--the residence time of
the blood in the cooling zone will be reduced, and the brain will
be chilled less deeply before the blood returns to the body core
and is re-warmed. However, power and fluid requirements are reduced
and selective cooling is still achieved. [0467] 2. Controlling the
temperature of the irrigating fluid to the lowest temperature that
does not damage the aerodigestive tract (e.g., between about
-20.degree. C. and 20.degree. C.). [0468] 3. Controlling the level
of fluid in the patients mouth by occasional adjustment of the flow
rate in the oral catheter/return line. This allows maximal fluid
recovery and even adjustment of cooling rate/selectivity by
incomplete wetting of the pharynx. [0469] 4. Intermittently
providing cooled liquid to the upper airway sufficient that such
that the controlling resistance to heat transfer is not convective
exchange between the patient and the irrigating fluid (e.g., about
0.2-5 l/min). [0470] 5. If a warming device is used (optional
because of low cooling power) Controlling the temperature of the
surface warming devices to not exceed about 40-42.degree. C. [0471]
6. Optionally applying the warming devices to the patient to warm
the surface (skin) of the patient. The warming device can comprise,
for example, one or more of a warming blanket, warming helmet,
warming of the face or neck posteriors(a maximum surface area is
preferred when a maximum gradient between brain and body is
desired).
[0472] The "maximum selectivity" method is differentiated from the
method of rapid brain cooling using naso-oro perfusion and head
immersion in dogs described by White et al. ("Rapid Selective
Brain-Cooling using Head Immersion and Naso-Oral Perfusion in Dogs,
Resuscitation 10:189-191, 1983), in that it does not immerse the
subject's head. Avoiding head immersion can provide improved
cooling selectivity. Selectivity is improved because the brain is
convectively shielded from surface cooling of the face and scalp,
but the blood large flow rates to these areas imply that a large
amount of cooled blood will be returning to the core, causing
systemic cooling. Avoiding head immersion is also helpful in
reducing liquid use and cooling power requirements. Avoiding head
immersion in ice water also avoids potential cosmetic effects to
the face neck and scalp. In addition, the system described employs
a disposable heat exchanger rather than ice, a sanitary disposable
fluid path, an oral catheter for return of fluid to a base unit
thermoelectric system, and feedback control of cooling and warming
based on at least the patient core temperature.
[0473] FIG. 15 illustrates a re-usable cooling system that is part
of the base unit, and that can be used to remove heat from the
disposable heat exchanger. FIG. 15 is a representative block
diagram showing one embodiment of the cooling system (the cooler)
itself. The cooler can be in thermal contact with a disposable heat
exchanger. The feedback control system can be configured so that
power to the thermoelectric system is modulated based on the
temperature of the fluid leaving the system.
[0474] An optional bypass valve arrangement is shown in FIG. 15.
The bypass valve can allow fluid to be recirculated before being
introduced into the patient. The bypass valve arrangement can also
be placed at other parts of the fluid circuit, such as at the
connection of the exit lines of the heat exchanger with the return
line. The thermoelectric system(s) can include one or more
individual thermoelectric elements arranged in an array, in thermal
contact with a thermally conductive element (platen) designed to
interface with the disposable heat exchanger. Although the platen
and heat exchanger can be physically touching and in good thermal
contact, they are desirably not in fluidic communication. The heat
sink(s) can be in thermal contact with the hot side of the
thermoelectric system and prevent the thermoelectric system form
over heating due to accumulation of heat removed from the heat
exchanger as well as internal generation when power is applied. A
variety of heat sinks may be used.
[0475] As discussed above, a variety of heat exchangers (e.g.,
plate, shell, tube, etc.) can be used to provide two or more
distinct paths for fluids. The cooling system and the heat
exchanger can be in thermal contact and physically touching, but
not in fluidic communication. Thus, heat exchange can be
accomplished while avoiding contamination of the cooling unit with
fluids that contact the patient.
[0476] In one example, the heat exchanger can contact the exchange
surfaces of the thermoelectric arrays of the cooling system in a
"sandwich like" configuration. A locking mechanism or locating
pins/datums can be provided to confirm proper location of the heat
exchanger within the cooling unit, and lights can be provided to
indicate correct placement or "ready" status. When powered, the
thermoelectric arrays remove heat from the exchange surfaces and
"pump" it towards the heat sinks, causing the heat sinks to warm,
and the fluid to cool. The power sent to the thermoelectric arrays
can be chosen so that the fluid is cooled to a temperature of 0 to
10.degree. C. generally but may be lower in some cases. Alternative
embodiments of the "sandwich" geometry feature can include, for
example, one-sided thermoelectric contact or two smaller heat
exchangers in tandem. In the case of 2 heat exchangers, one could
be configured to serve the nasal area and one to serve the
esophageal area. These heat exchangers can interface with separate
cooling units or have distinct slots in one cooling unit. FIG. 16
illustrates an exemplary cooling system. Although FIG. 16
illustrates the thermoelectric array in thermal communication with
a "fanless" heat sink, other heat sinks could be used, such as heat
sinks that utilize finned areas and/or fans.
[0477] FIG. 17 illustrates a block diagram showing a simple
feedback control loop designed to control a surface warming device
based on the temperature at the interface between the device and
the skin. The current and voltage (I, V) to the warming device can
be modulated based on the difference between temperature of the
device at the patient's skin and the set point provided to the
controller. Of course, if desired, measurements at more than one
location may be used.
[0478] A heat sink can comprise finned and fanned heat sinks
typical of thermoelectric devices, where fans are used to force air
over the hot surfaces, and the area for exchange is enhanced
through the addition of fins. Alternatively, the heat can be
removed using a fanless heat sink, by employing an arrangement
similar to that of FIG. 15. The heat from the thermoelectric arrays
can warm a reservoir of fluid contained in a sealed compartment
with ample headspace. If the fluid is chosen with a boiling point
in the range of 30 to 60.degree. C., the current and voltage of the
thermoelectric arrays can be chosen to provide a "hot side"
temperature in this range. This will result in the liquid boiling
as more heat is added to the heat sink reservoir side while the
side contacting the single use heat exchanger is being cooled. The
resulting vapor in the heat sink reservoir compartment can rise
through the head space into the condensation section of the heat
sink where it will condense as it encounters cooler temperatures.
The heat sink fluid can continue to reflux through the heat sink
compartment and thus dissipate the heat from the thermoelectric
devices into the environment.
[0479] Such a heat sink can be significantly easier to clean in the
case of contamination (by a spill, for example) than a finned and
fanned heat sink. Also, during ordinary operation, the system can
desirably accumulate and spread less dust and dirt than a fanned
system. Additional advantages of fanless arrangements in a hospital
environment include improved reliability and reduced noise. Also,
further the condensation sections can be arranged to act as handles
for the unit.
[0480] The walls of the heat sinks described herein are preferably
made of a highly thermally conductive material (such as a metal)
that is resistant to common chemical sterilizing solutions (such as
ethanol in water, ammonium salts, etc). For example, stainless
steel or other metals, with or without protective coatings, can be
used.
[0481] In other embodiments, cooling techniques that are not based
on thermoelectric arrays, such as a conventional refrigeration
system, ice bath or endothermic chemical reaction, can be used.
[0482] The heat exchanger that interfaces with the cooling system
is part of the patient interface kit and intended to be disposable.
The heat exchanger is sized to provide about 5 up to 300 W of heat
exchange at a flow rate of about 0.2-10 liters per minute. The
actual amount of heat exchange depends on the temperature of the
incoming fluid. The heat exchanger provides a serpentine flow path
for the fluid to be cooled, as is typical of most heat exchanger
designs. The heat exchanger is preferably constructed of a highly
thermally conductive material, such as a metal, with aluminum,
stainless steel, or copper being suitable choices. A box-like
geometry with an internal channel of rectangular cross section is
envisioned. The diameter or hydraulic diameter of the fluid path
can be about 0.2-6 cm, with length of the flow path chosen to
provide 100 to 300 W of heat exchange capability. Typical
dimensions of the overall heat exchanger might be about 20 to 40 cm
wide and 10 to 30 cm high, with a thickness of about 2 to 8 cm.
These values are based on a simple serpentine fluid path, more
compact arrangements are possible as the path becomes more
tortuous.
[0483] The disposable heat exchanger can have one inlet for
accepting fluid from the reservoir and one or more outlets for
fluid to exit. In one example, one outlet for the nasal pump is
provided and one outlet for the esophageal pump is provided. The
portion of the heat exchanger near the inlet and outlet ends can be
expanded slightly to accommodate fittings and connectors for
incoming and outgoing lines. A bypass line may also be included
with the disposable heat exchanger to allow recirculation of fluid
through the heat exchanger while the device is in standby mode this
feature is optional. In some embodiments, the walls of the heat
exchanger that are not contacting the cooling elements of cooling
unit will be insulated to reduce condensation and loss of cold to
the environment
[0484] As discussed above, various cooling fluids can be introduced
into the aerodigestive tract. When maximum cooling rates and
antibacterial properties are desired, the fluid formulations
disclosed above can be desirable. When an extensive period of
irrigation is desired, it can be advantageous to select an
irrigating fluid that has an osmolality roughly equivalent to that
in the tissues surrounding the aerodigestive tract so that water is
not needlessly removed or added to the patient. To achieve osmotic
balance, for example, a fluid formulation similar to that normally
encountered by the cells lining the walls of the pharynx and
esophagus can be desirable.
[0485] In one example, the formulation can be one with an
electrolyte composition similar to that of ordinary saliva,
including some or all of the following cations: sodium at about
1-40 mmol/l, potassium at about 5 to 60 mmol/l, calcium at about
0.5-5 mmol/l, magnesium at less than 1 mmol/l, and the following
anions: chloride at 1-200 mmol/l, bicarbonate at 1-100 mmol/l,
phosphate at less than 50 mmol/l and iodine at less than 10 mmol/l.
This mixture can minimize chemical exchange between the body and
the irrigation fluid by avoiding large osmolality or concentration
gradients between the cells bordering the aerodigestive tract and
the irrigating fluid. It should be noted, however, that the match
need not be exact since the re-circulated fluid will equilibrate
with the patient.
[0486] A slightly hypotonic formulation can also be useful because
it will keep the total volume in the fluid circuit roughly
constant. In more sophisticated formulations, the irrigation fluid
might also be used to replace some of the mechanical and
immunological functions of fluids found in the aerodigestive tract
such as swallowed saliva, and other formulations can be created by
adding proteins commonly found in saliva such as mucins, amylases,
etc. A special dose of mucus like fluid could be added just before
extubation to facilitate removal of the tubes.
[0487] Table 8 below identifies symbols used herein and in the
figures.
TABLE-US-00008 TABLE 8 Symbol Meaning Note Error signal, indicating
the Used by controllers in difference between the feedback control
loops measured value and the programmed set point Flow 1 Fluid flow
rate in the or F1 nasal line Flow 2 Fluid flow rate in the or F2
esophageal line TM A temperature measure- ment device FM A flow
rate measurement device Time A commanded time in Typically used to
describe seconds and/or duty cycle the amount of warming or e.g.
minutes/hour pumping needed T.sup.setpoint Set point temperature
Typically set point for patient commanded by the user rectal
temperature, but could be any single or multivariable measurement
even, intracranial pressure, ICP T.sup.fluid Temperature of the
fluid leaving the cooling unit, and about to enter the patient
T.sup.measured Measured temperature Typically measurement for
patient rectal temperature returned to the controller, but could be
any single or multivariable measurement even, intracranial
pressure, ICP I, V Electric power (watts) going to coolers or
warmers q.sup.d Heat exchanged with the environment or generated by
metabolism Q Total heat exchanged with all sources other than the
cooler Qw Heat supplied by the warmer
[0488] The amount of warming needed can be determined by one or
more of the following: monitoring the patients core temperature,
considering the amount of heat being removed from the patient as
determined by heat balance on incoming and outgoing fluid, energy
balance on the thermoelectric cooling unit, empirical or
semi-empirical relationships between multiple patient temperature
measurements, and/or mathematical models. As described elsewhere,
the location of warming can vary and can include, for example, the
scalp, the arms, the legs, or other body surfaces. The means of
warming can include circulating liquid blanket(s), hydrogel pad(s)
with circulating liquids, forced air, heat lamp(s), electric
blanket(s), or other suitable heat generating devices. In the case
where the warming device employs circulating liquid, the warming
power delivered to the patient can be estimated by monitoring the
incoming and return temperatures of the warming fluid after
accounting for other heat losses.
[0489] In another embodiment, a hybrid cooling system can be
provided. The hybrid cooling system can include a cooling system
configured to deliver (a) free flowing fluid to cool the nasal
cavity as described herein and (b) balloon-contained fluid in which
fluid can be circulated to cool the esophagus or at least a portion
of the esophagus.
[0490] The balloon can be arranged around a catheter in an annular
or partially annular fashion. An annular balloon can function to
confine emesis to a large lumen of the catheter as described
elsewhere herein. Alternatively, the balloon can be formed in a
non-annular manner, such as with an elongated side balloon that
makes good thermal contact with the arteries. A center lumen of the
esophageal catheter can still function to provide stomach access
and a cuff can be provided to restrict entry of emesis into the
esophagus. A cuff tube can protect the lungs and suction can be
applied just above the cuff to prevent stagnation as described in
more detail in other embodiments.
[0491] If desired, additional fluid can be added to wash the
esophagus and make good thermal contact. Fluid can exit at the
mouth or, alternatively can be "dropped" into the stomach. Instead
of adding additional fluid, fluid can be permitted to drip down
from the nasal area to the esophagus or a portion of the
esophagus.
[0492] The fluid in the balloons can be used to either maintain the
esophagus in a cooled state or, alternatively, to re-warm the
patient as needed.
[0493] In another embodiment, a system can be provided with a
balloon that has recirculating cold fluid in the nose and free
flowing fluid in the esophagus. Additional fluid can be added
through an end lumen to wash the nasal cavity and make good thermal
contact (e.g., like a "thermal grease"). The free flowing fluid can
pile up in the esophagus and be removed through, for example, an
oral return line. As in other embodiments, the lungs can be
protected with a cuffed tube and suction just above the cuff can
reduce/prevent stagnation.
[0494] In another embodiment, separate balloons can be provided in
the nose and in the esophagus with re-circulating liquid for
cooling. Additional fluid can be provided for
conductivity/flushing. Again, as in other embodiments, the lungs
can be protected with a cuffed tube and suction just above the cuff
can reduce/prevent stagnation.
[0495] Although the methods and devices have been described in
association with certain theories of their operation, the invention
is not to be limited by those theories. To the extent that the
invention can be understood in terms of the described structures
and methods, the claims do not incorporate theories of operation
unless the claims clearly indicate otherwise.
[0496] Other systems and methods can be used to help achieve and/or
maintain a brain to body core temperature gradient. Such methods
can be used along with the devices, systems, and methods previously
described. For example, the devices, systems, and methods of the
present invention can be used along with methods to reduce cerebral
blood flow (e.g., 0 to 50% less than baseline). Reducing cerebral
blood flow can have several advantages, such as, for example,
increasing the time that the blood is in contact with anatomical
regions cooled by the present methods, systems, and devices (e.g.,
reducing the temperature of the blood entering the brain) and
reducing thermal interdependence between the brain and the body
core (e.g., by increasing the amount of time cooled blood is in the
brain and decreasing the amount of blood entering the brain in a
given period, thus decreasing the amount of cooled blood returned
to the core in relation to total cardiac output).
[0497] Various methods to reduce cerebral blood flow can be used
with the present invention. For example, selective cooling the
brain, itself, can result in decreased cerebral blood flow.
However, in the event that selective brain cooling increases
cerebral blood flow, other measures (e.g., described below) can be
taken to decrease cerebral blood flow. Further, maximizing direct
conductive cooling of inferior aspects of the brain (e.g., by
adding surface active agents to the cooling fluid and/or decreasing
cooling fluid residence time in sinuses) and/or maximizing cooling
of the common carotid and vertebral arteries can reduce cerebral
blood flow. Induced systemic cooling of the brain and the body in
humans can also decrease cerebral blood flow.
[0498] As another example, various sedation methods can be used to
decrease blood flow rate. Further, a method to reduce cerebral
blood flow can comprise reducing cerebral perfusion pressure, for
example, by decreasing blood pressure (systolic and diastolic),
shunting blood to the body core (e.g., away from brain and
meningeal arteries), and/or warming the scalp. Additionally, brief
bursts or episodes of systemic cooling can reduce blood flow rate
to the brain (e.g., by reducing brain metabolism). Still another
example of reducing blood flow rate to the brain can be to induce
hypocarbia or hyperventilation (e.g., by reduction of arterial
CO2), which acts to reduce cerebral perfusion, narrow cerebral
arteries, increase resistance to cerebral blood flow, and/or reduce
cerebral blood volume.
[0499] In other embodiments, cerebral blood flow of a patient can
be decreased by administering medications and/or agents to the
patient. For example, a subject can be administered barbiturates
(e.g., thiopental drip, phenobarbital, pentobarbital, methohexital,
etc.), benzodiazepines (e.g., Versed, Ativan, Valium), propofol,
clonidine, lidocaine, etomidate, caffeine, alcohols (e.g.,
ethanol), cocaine, beta-blockers (e.g., labetalol), anti-migraine
medications (e.g., triptans, ergotamines, etc.), inhaled gas (e.g.,
isofluorane), narcotics, systemic vasoconstrictors (e.g.,
phenylephrine), and other select medications and/or agents. Such
agents can lead to a narrowing of cerebral arteries, a reduction in
cerebral blood volume, and/or a resistance to cerebral blood flow.
Appropriate doses of such medications and/or agents will be
understood by those of skill in the art.
[0500] In some instances, increasing intracranial pressure (e.g.,
by lying a subject's head and body flat, by increasing positive
end-expiratory pressure using the ventilator) from low pressure
levels induced by cooling therapy can also assist in reducing
cerebral blood flow. Other methods of decreasing cerebral blood
flow can include reducing heart rate and reducing systemic vascular
resistance in relation to cerebral vascular resistance (e.g., with
vasodilators and/or warming the skin). A number of these methods
also decrease metabolic demand of the brain, which can further lead
to reduced cerebral blood flow.
EXAMPLES
[0501] The following includes two examples of use of the present
devices, systems, and methods, and various examples of features
that can be included in various embodiments of the present methods
and apparatuses. Examples 1 and 2 comprise recirculating chiller
units and plate heat exchanges to cool fluid (e.g., as depicted in
FIGS. 23A, 23B, 24A, and 25A). Fluid was withdrawn from a 10 L
fluid supply reservoir using peristaltic pumps (Cole-Parmer
computer-controlled digistaltic pump drive). Fluid was pumped
through two heat exchangers prior to passing the fluid through the
plurality of catheters. The heat exchangers were coupled to one or
more recirculating chiller unites (e.g., Polyscience benchtop
chillers) to cool the heat exchangers. Fluid was recovered from the
patient (e.g., via vacuum suction) through oral and/or tracheal
return lumens in fluid communication with the fluid supply
reservoir.
[0502] In each example, the following procedures were used.
[0503] 1. Mechanical Ventilation [0504] a. Volume Control: Vt=8
ml/kg, Rate=10/min, PEEP=5, FiO2=30% [0505] b. ETCO2: 30-35 Torr
[0506] c. pH: 7.35-7.45 [0507] d. O2 sat >96% throughout
study
[0508] 2. Catheters [0509] a. Esophogeal catheter: 3-lumen catheter
[0510] i. Provided access to the stomach to permit gas and fluid to
escape stomach. [0511] ii. Provided ability to inflate a balloon
within esophagus to prevent cooling fluid from entering stomach.
[0512] iii. Provided cooled liquid to the lower portion of the
esophagus. [0513] b. Endotracheal catheter: 3-lumen catheter [0514]
i. Provided access to the lungs to permit air to enter and exit the
lungs. [0515] ii. Provided ability to inflate a balloon within
trachea to prevent cooling fluid from entering the lungs. [0516]
iii. Provided ability to remove cooling liquid from trachea. [0517]
c. Two Nasal Catheters: Provided cooling fluid into aerodigestive
tract. [0518] d. Oral Catheter: Provided ability to remove fluid
accumulating in mouth.
[0519] 3. Control System: [0520] a. System On/Off [0521] b. Body
Set Point [0522] c. Pump 1 Speed [0523] d. Pump 2 Speed [0524] e.
Pump Enable On/Off
Example 1
[0525] A 76 kg pig was placed supine and was systemically warmed
using a small Gaymar circulating water blanket and forced hot
air.
[0526] Four temperature probes were active. A needle probe was
inserted into the animal's brain. Two catheter probes were inserted
into the aorta and inferior vena cava, respectively. Also, a rectal
temperature probe was used to monitor core temperature. Temperature
probes were controlled using LabView, and pumps were controlled
manually (i.e., the system was run in "open loop" mode). A fluid
schematic of the system used is depicted in FIG. 23A, and an
electrical schematic is depicted in FIG. 23B. After a series of
set-up tests, the pig was rewarmed, and the cooling fluid was
refilled. Pumps were set to 300 RPM, and cool fluid was pumped
through catheters for approximately 120 minutes. The pig's initial
temperatures were: Brain--38.0.degree. C.; Aorta--38.3.degree. C.;
Vena Cava--38.4.degree. C.; and Rectal--38.3.degree. C. A graphical
representation of results is depicted in FIG. 23C, and Table 9
displays parameters associated with this trial.
TABLE-US-00009 TABLE 9 Parameter Value Time from `Start` to
33.degree. C. Brain 8.68 min Initial 300 RPM cooling Brain
1.degree. C. 3.04 min Min time to cool Brain 1.degree. C. 1.17 min
Initial 300 RPM cooling Core 1.degree. C. 26.24 min Min Rewarming
time Brain 1.degree. C. 2.28 min Min Rewarm time Core 1.degree. C.
48.1 min Max gradient 9.7.degree. C. Lowest T brain 27.09.degree.
C. Lowest T core 36.13.degree. C.
[0527] The pig was rewarmed, and the cooling fluid was refilled.
Pumps were set to 600 RPM, and cool fluid was pumped through
catheters for approximately 32.45 minutes. The pig's initial
temperatures were: Brain--38.1.degree. C.; Aorta--38.3.degree. C.:
Vena Cava--38.5.degree. C.; and Rectal 38.1.degree. C. A graphical
representation of results is depicted in FIG. 23D up to a time of
approximately 32.45 minutes, and Table 10 displays parameters
associated with this trial.
TABLE-US-00010 TABLE 10 Parameter Value Time from `Start` to
33.degree. C. Brain 8.15 min Initial 600 RPM cooling Brain
1.degree. C. 2.01 min Min time too cool brain 1.degree. C. 1.18 min
Initial core cooling 1.degree. C. 26.75 min Min rewarming time core
NA Min rewarming time brain NA Max gradient 8.95.degree. C. Lowest
T brain 28.06.degree. C. Lowest T core 36.0.degree. C.
[0528] The pump speed was reduced mid-cycle from 600 RPM to 300 RPM
at approximately 32.45 minutes, and cool fluid was pumped through
catheters for approximately 30 more minutes. A graphical
representation of results is depicted beginning at approximately
32.45 minutes in FIG. 23D, and Table 11 displays parameters
associated with this trial.
TABLE-US-00011 TABLE 11 Parameter Value Min brain temp after change
to 300 RPM 28.3 Max gradient after change to 300 RPM 8.36 Min
rewarming time core NA Min rewarming time brain 1.degree. C. 1.53
min
[0529] These tests demonstrate that a variety of flow rates can be
used to accomplish cooling, that cooling is rapid, that cooling is
selective, that the brain returns to its former state once cooling
ends, and that the results are reproducible.
Example 2
[0530] In Example 2, a pig of similar size was used. The cooling
apparatus was similar to that used in the previous example;
however, flow meters and a vacuum regulator were included. A
schematic representation of the fluid system of Example 2 is
depicted in FIG. 24A. The electrical system did not change from
that in Example 1. A graphical representation of results of Example
2 are depicted in FIG. 24B.
[0531] As depicted at minutes 120 to 180 of FIG. 24B, body core
temperature was substantially maintained and/or increased with a
counter warming device, while brain temperature decreased (e.g.,
increasing a brain to body core temperature gradient). A maximum
brain to body core temperature gradient of approximately
10.8.degree. C. was achieved. Addition of propofol as an anesthetic
assisted in decreasing brain temperature by, for example,
decreasing blood flow to the brain and/or allowing deeper
equilibration of blood in the large arteries of the neck (e.g., by
decreasing flow rate and velocity and increasing residence time).
However, as described above, a number of other anesthetics can also
be used.
[0532] In view of the many possible embodiments to which the
principles of the disclosed invention may be applied, it should be
recognized that the illustrated embodiments are only preferred
examples of the invention and should not be taken as limiting the
scope of the invention. Rather, the scope of the invention is
defined by the following claims. We therefore claim as our
invention all that comes within the scope and spirit of these
claims.
[0533] The above specification and examples provide a complete
description of the structure and use of exemplary embodiments.
Although certain embodiments have been described above with a
certain degree of particularity, or with reference to one or more
individual embodiments, those skilled in the art could make
numerous alterations to the disclosed embodiments without departing
from the scope of this invention. As such, the various illustrative
embodiments of the present devices are not intended to be limited
to the particular forms disclosed. Rather, they include all
modifications and alternatives falling within the scope of the
claims, and embodiments other than the one shown may include some
or all of the features of the depicted embodiment. For example,
components may be combined as a unitary structure and/or
connections may be substituted. Further, where appropriate, aspects
of any of the examples described above may be combined with aspects
of any of the other examples described to form further examples
having comparable or different properties and addressing the same
or different problems. Similarly, it will be understood that the
benefits and advantages described above may relate to one
embodiment or may relate to several embodiments.
* * * * *