Note: Descriptions are shown in the official language in which they were submitted.
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PATIENT TEMPERATURE REGULATION METHOD AND
APPARATUS
15
STATEMENT REGARDING FEDERALLY SPONSORED
RESEARCH OR DEVELOPMENT
Not Applicable
BACKGROUND OF THE INVENTION
Field of the Invention - The present invention relates generally to the
lowering
and control of the temperature of the human body. More particularly, the
invention
relates to a method and intravascular apparatus for cooling the body without
the
adverse consequences associated with prior methods of total body cooling. The
invention also relates to a method and intravascular apparatus for cooling the
body
without causing thermoregulatory suppression of the cooling.
Background Information - Organs in the human body, such as the brain,
kidney and heart, are maintained at a constant temperature of approximately 37
C.
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Hypothermia can be clinically defined as a core body temperature of 35 C or
less.
Hypothermia is sometimes characterized further according to its severity. A
body core
temperature in the range of 330 C to 35 C is described as mild hypothermia. A
body
temperature of 28 C to 32 C is described as moderate hypothermia. A body
core
temperature in the range of 24 C to 28 C is described as severe hypothermia.
Hypothermia is uniquely effective in reducing brain injury caused by a variety
of
neurological insults and may eventually play an important role in emergency
brain
resuscitation. Experimental evidence has demonstrated that cerebral cooling
improves
outcome after global ischemia, focal ischemia, or traumatic brain injury. For
this reason,
hypothermia may be induced in order to reduce the effect of certain bodily
injuries to the
brain as well as other organs.
Cerebral hypothermia has traditionally been accomplished through whole body
= cooling to create a condition of total body hypothermia in the range of
20 C to 30 C.
The currently-employed techniques and devices used to cause total body
hypothermia
lead to various side effects. In addition to the undesirable side effects,
present methods of
= administering total body hypothermia are cumbersome.
Catheters have been developed which are inserted into the bloodstream of the
patient in order to induce total body hypothermia. For example, U.S. Patent
No.
3,425,419 to Dato describes a method and apparatus of lowering and raising the
temperature of the human body. Dato induces moderate hypothermia in a patient
using a
rigid metallic catheter. The catheter has an inner passageway through which a
fluid, such
as water, can be circulated. The catheter is inserted through the femoral vein
and then
through the inferior vena cava as far as the right atrium and the superior
vena cava. The
Dato catheter has an elongated cylindrical shape and is constructed from
stainless steel.
By way of example, Dato suggests the use of a catheter approximately 70 cm in
length
and approximately 6 mm in diameter. Thus, the Dato device cools along the
length of a
very elongated device. Use of the Dato device is highly cumbersome due to its
size and
lack of flexibility.
U.S. Patent No. 5,837,003 to Ginsburg also discloses a method and apparatus
for
controlling a patient's body temperature. In this technique, a flexible
catheter is inserted
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=
into the femoral artery or vein or the jugular vein. The catheter may be in
the form of a
balloon to allow an enhanced surface area for heat transfer. A thermally
conductive metal
foil may be used as part of a heat-absorbing surface. This device fails to
disclose or teach
use of any ability to enhance heat transfer. In addition, the disclosed device
fails to
disclose temperature regulation.
Therefore, a practical method and apparatus that lowers and controls the
temperature of the human body satisfies a long-felt need.
BRIEF SUMMARY OF THE INVENTION
In one aspect, the apparatus of the present invention can include a heat
transfer
element that can be used to apply cooling to the blood flowing in a large vein
feeding the
heart. An optional heating element may be used to supply warming to a portion
of the
remainder of the body to provide comfort to the patient and to allow a low
target
hypothermic temperature to be achieved. The heating element may be applied
before or
after a target temperature is achieved. The wanning operation can be
accomplished by
means of local heating of the vein or artery with an external heat applicator
or by means
of substantially whole body warming with a heating blanket. The warming
operation can
be accomplished per se or in combination with thermoregulatory drugs.
The heat transfer element, by way of example only, includes first and second
elongated, articulated segments, each segment having a mixing-inducing
exterior surface.
A flexible joint can connect the first and second elongated segments. An inner
lumen
may be disposed within the first and second elongated segments and is capable
of
transporting a pressurized working fluid to a distal end of the first
elongated segment. In
addition, the first and second elongated segments may have a mixing-inducing
interior
surface for inducing mixing within the pressurized working fluid. The mixing-
inducing
exterior surface may be adapted to induce mixing within a blood flow when
placed within
an artery or vein. In one embodiment, the flexible joint includes a bellows
section that
also allows for axial compression of the heat transfer element as well as for
enhanced
flexibility. In alternative embodiments, the bellows section may be replaced
with flexible
tubing such as small cylindrical polymer connecting tubes.
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In one embodiment, the mixing-inducing exterior surfaces of the heat transfer
element include one or more helical grooves and ridges. Adjacent segments of
the heat
transfer element can be oppositely spiraled to increase mixing. For instance,
the first
elongated heat transfer segment may include one or more helical ridges having
a counter-
clockwise twist, while the second elongated heat transfer segment includes one
or more
helical ridges having a clockwise twist. Alternatively, of course, the first
elongated heat
transfer segment may include one or more clockwise helical ridges, and the
second
elongated heat transfer segment may include one or more counter-clockwise
helical
ridges. The first and second elongated, articulated segments may be formed
from highly
conductive materials such as metals.
The heat transfer device may also have a supply catheter with an inner
catheter
lumen coupled to the inner lumen within the first and second elongated heat
transfer
segments. A working fluid supply configured to dispense the pressurized
working fluid
may be coupled to the inner catheter lumen or alternatively to the supply
catheter. The
working fluid supply may be configured to produce the pressurized working
fluid at a
temperature of about 0 C and at a pressure below about 5 atmospheres of
pressure.
In yet another alternative embodiment, the heat transfer device may have three
or
more elongated, articulated, heat transfer segments each having a mixing-
inducing
exterior surface, with additional flexible joints connecting the additional
elongated heat
transfer segments. In one such embodiment, by way of example only, the first
and third
elongated heat transfer segments may include clockwise helical ridges, and the
second
elongated heat transfer segment may include one or more counter-clockwise
helical
ridges. Alternatively, of course, the first and third elongated heat transfer
segments may
include counter-clockwise helical ridges, and the second elongated heat
transfer segment
may include one or more clockwise helical ridges.
The mixing-inducing exterior surface of the heat transfer element may
optionally
include a surface coating or treatment to inhibit clot formation. A surface
coating may
also be used to provide a degree of lubricity to the heat transfer element and
its associated
catheter.
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The present invention is also directed to a method of inducing hypothermia in
the
body by inserting a flexible, conductive cooling element into a vein that is
in pressure
communication with the heart, e.g., the superior or inferior vena cavae or
both. The vena
cavae may be accessed via known techniques from the jugular vein or from the
subclavian or femoral veins, for example. The heat transfer element in one or
both vena
cavae may then cool virtually all the blood being returned to the heart. The
cooled blood
enters the right atrium at which point the same is pumped through the right
ventricle and
into the pulmonary artery to the lungs where the same is oxygenated. Due to
the heat
capacity of the lungs, the blood does not appreciably warm during oxygenation.
The
cooled blood is returned to the heart and pumped to the entire body via the
aorta. Thus,
cooled blood may be delivered indirectly to a chosen organ such as the brain.
This
indirect cooling is especially effective as high blood flow organs such as the
heart and
brain are preferentially supplied blood by the vasculature. A warming blanket
or other
warming device may be applied to portions of the body to provide comfort to
the patient
and to inhibit therrnoregulatory responses such as vasoconstriction.
Thermoregulatory
drugs may also be so provided for this reason.
The method further includes circulating a working fluid through the flexible,
conductive cooling element in order to lower the temperature of the blood in
the vena
cava. The flexible, conductive heat transfer element preferably absorbs more
than about
150 or 300 Watts of heat.
The method may also include inducing mixing within the free stream blood flow
within the vena cava. It is noted that a degree of turbulence or mixing is
generally
present within the vena cava anyway. The step of circulating may include
inducing
mixing in the flow of the working fluid through the flexible, conductive heat
transfer
element. The pressure of the working fluid may be maintained below about 5
atmospheres of pressure.
The present invention also envisions a method for inducing therapeutic
hypothermia in the body of a patient which includes introducing a catheter,
with a cooling
element, into a vena cava supplying the heart, the catheter having a diameter
of about 18
mm or less, inducing mixing in blood flowing over the cooling element, and
lowering the
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temperature of the cooling element to remove heat from the blood to cool the
blood. In
one embodiment, the cooling step removes at least about 150 Watts of heat from
the
blood. In another embodiment, the cooling step removes at least about 300
Watts of heat
from the blood.
The mixing induced may result in a Nusselt number enhancement of the flow of
between about 5 and 80.
In another aspect of the method, the invention is directed to a method of
lowering
the temperature of the body while prohibiting intervention of the body's
thermoregulatory
responses. Steps of the method may include delivering a drug to lower the
thermoregulatory setpoint of the body such that thermoregulatory responses,
including
shivering and vasoconstriction, are not triggered above a certain temperature,
wherein the
certain temperature is lower than normal body temperature. The temperature of
the blood
in a major vein such as the vena cavae is then lowered to induce hypothermia
in the body.
The thermoregulatory drugs provide patient comfort. If even lower body
temperatures
are desired or required, heating blankets may be provided to further ensure
patient
comfort. Generally, for one degree of body core cooling, the heating blanket
should be 5
C above the skin temperature to provide patient comfort. However, the
temperature of
the blanket should generally not exceed 42 C.
Advantages of the invention are numerous. Patients can be provided with the
beneficial aspects of hypothermia without suffering the deleterious
consequences of the
prior art. The procedure can be administered safely and easily. Numerous
cardiac and
neural settings can benefit by the hypothermic therapy. For example, ischemia
and re-
stenosis can be minimized. Other advantages will be understood from the
following.
The novel features of this invention, as well as the invention itself, will be
best
understood from the attached drawings, taken along with the following
description, in
which similar reference characters refer to similar parts, and in which:
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In another aspect of the present invention, there is provided a system
for cooling a patient's body intravascularly, comprising: a flexible catheter
insertable
into a vein; a flexible heat transfer element attached to a distal end of the
flexible
catheter, the flexible heat transfer element including a plurality of heat
transfer
segments connected by flexible joints; and a heating blanket for applying heat
to a
selected portion of the patient's body, wherein the heating blanket employs a
warm-
air blower and includes air channels for evenly distributing warm air to the
surface
area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling a patient's body intravascularly, said system
comprising a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a plurality of flexible heat transfer
segments
connected by flexible joints, the heat transfer segments comprising a
plurality of
surface irregularities shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularities comprising a helical ridge and a helical groove
formed on
each heat transfer segment, wherein said catheter is configured for insertion
through
the patient's vascular system, and the heat transfer element is configured for
(i)
placement in the patient's vein that drains into the patient's heart, (ii) the
circulation of
fluid therethrough, and (iii) the transfer of heat between blood in the vein
and the heat
transfer element, and further comprising the use of a heating blanket to
deliver heat
to a substantial portion of the surface area of the patient, wherein the
heating blanket
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
platelet aggregation in a blood vessel in which blood is flowing, said system
comprising a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a plurality of flexible heat transfer
segments
connected by flexible joints, the heat transfer segments comprising a
plurality of
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'
,
64869-1327D
surface irregularities shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularities comprising a helical ridge and a helical groove
formed on
each heat transfer segment, wherein said catheter is configured for insertion
through
the vascular system of the patient, and the heat transfer element is
configured for (i)
placement in the patient's blood vessel in which blood is flowing, (ii) the
circulation of
fluid therethrough and (iii) the transfer of heat between blood in the vessel
and the
heat transfer element, whereby upon said use the blood is cooled and platelet
aggregation is substantially reduced, and further comprising the use of a
heating
blanket to deliver heat to a substantial portion of the surface area of the
patient,
wherein the heating blanket employs a warm-air blower and includes air
channels for
evenly distributing warm air to the surface area of the selected portion of
the patient's
body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
dependence on drug therapies in treating insults or injuries resulting in
ischemia, said
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a plurality of flexible heat
transfer segments
connected by flexible joints, the heat transfer segments comprising a
plurality of
surface irregularities shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularities comprising a helical ridge and a helical groove
formed on
each heat transfer segment, wherein said catheter is configured for insertion
through
the vascular system of the patient, and the heat transfer element is
configured for (i)
placement in the patient's blood vessel in which blood is flowing, (ii) the
circulation of
fluid therethrough and the transfer of heat between the blood in the vessel
and the
heat transfer element, whereby upon said use the blood is cooled, and further
comprising the use of a heating blanket to deliver heat to a substantial
portion of the
surface area of the patient, wherein the heating blanket employs a warm-air
blower
and includes air channels for evenly distributing warm air to the surface area
of the
selected portion of the patient's body.
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In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
dependence on drug therapies in treating insults or injuries resulting in
ischemia, said
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a plurality of flexible heat
transfer segments
connected by flexible joints, the heat transfer segments comprising a
plurality of
surface irregularities shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularities comprising a helical ridge and a helical groove
formed on
each heat transfer segment, wherein said catheter is configured for insertion
through
the vascular system of the patient, and the heat transfer element is
configured for (i)
placement in the patient's vein, said vein being selected from superior vena
cava,
inferior vena cava, or a combination thereof, (ii) the circulation of fluid
therethrough,
and (iii) the transfer of heat between the blood in the vein and the heat
transfer
element, whereby upon said use at least one of platelet aggregation, oxygen
demands, and the metabolic rate of the heart is reduced or bradycardia is
induced,
and further comprising the use of a heating blanket to deliver heat to a
substantial
portion of the surface area of the patient, wherein the heating blanket
employs a
warm-air blower and includes air channels for evenly distributing warm air to
the
surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
stenoses recurring following angioplasty, said system comprising a catheter
having a
heat transfer element attached to a distal end thereof, the heat transfer
element
having a plurality of flexible heat transfer segments connected by flexible
joints, the
heat transfer segments comprising a plurality of surface irregularities shaped
and
arranged to create mixing in surrounding fluid, and the surface irregularities
comprising a helical ridge and a helical groove formed on each heat transfer
segment, wherein said catheter is configured for insertion through the
vascular
system of the patient, and the heat transfer element is configured for (i)
placement in
the patient's blood vessel, (ii) the circulation of fluid therethrough and
(iii) the transfer
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of heat between blood in the vessel and the heat transfer element, whereby
upon
said use the blood and the blood vessel wall are cooled, and further
comprising the
use of a heating blanket to deliver heat to a substantial portion of the
surface area of
the patient, wherein the heating blanket employs a warm-air blower and
includes air
channels for evenly distributing warm air to the surface area of the selected
portion of
the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
reperfusion injury following a reflow operation on a blood vessel of the
patient, said
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a plurality of flexible heat
transfer segments
connected by flexible joints, the heat transfer segments comprising a
plurality of
surface irregularities shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularities comprising a helical ridge and a helical groove
formed on
each heat transfer segment, wherein said catheter is configured for insertion
through
the vascular system of the patient, and the heat transfer element is
configured for (i)
placement in the patient's blood vessel, (ii) the circulation of fluid
therethrough and
(iii) the transfer of heat between the blood in the vessel and the heat
transfer
element, whereby upon said use the blood in the vessel is cooled, and further
comprising the use of a heating blanket to deliver heat to a substantial
portion of the
surface area of the patient, wherein the heating blanket employs a warm-air
blower
and includes air channels for evenly distributing warm air to the surface area
of the
selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling a patient's body intravascularly and a drug,
said
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a plurality of flexible heat
transfer segments
connected by flexible joints, the heat transfer segments comprising a
plurality of
surface irregularities shaped and arranged to create mixing in surrounding
fluid, and
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the surface irregularities comprising a helical ridge and a helical groove
formed on
each heat transfer segment, wherein said catheter is configured for insertion
through
the patient's vascular system, and the heat transfer element is configured for
(i)
placement in the patient's vein that drains into the patient's heart, (ii) the
circulation of
fluid therethrough and is (iii) the transfer of heat between blood in the vein
and the
heat transfer element, and further comprising the use of a heating blanket to
deliver
heat to a substantial portion of the surface area of the patient, wherein the
heating
blanket employs a warm-air blower and includes air channels for evenly
distributing
warm air to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided a system
for heating a patient's body intravascularly, comprising: a flexible catheter
insertable
into a vein; and a flexible heat transfer element attached to a distal end of
the flexible
catheter, the flexible heat transfer element including a plurality of flexible
heat transfer
segments connected by flexible joints, wherein the heat transfer segments
comprise
a plurality of surface irregularities, the surface irregularities being shaped
and
arranged to create mixing in surrounding fluid, and the surface irregularities
comprising a helical ridge and a helical groove formed on each heat transfer
segment; a heating blanket for applying heat to a selected portion of the
patient's
body, wherein the heating blanket employs a warm-air blower and includes air
channels for evenly distributing warm air to the surface area of the selected
portion of
the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for heating a patient's body intravascularly, said system
comprising a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a plurality of flexible heat transfer
segments
connected by flexible joints, the heat transfer segments comprising a
plurality of
surface irregularities shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularities comprising a helical ridge and a helical groove
formed on
each heat transfer segment, wherein said catheter is configured for insertion
through
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the vascular system, and the heat transfer element is configured for (i)
placement in
the patient's vein that drains into the heart of the patient, (ii) the
circulation of fluid
therethrough and (iii) the transfer of heat between blood in the vein and the
heat
transfer element, and further comprising the use of a heating blanket to
deliver heat
to a substantial portion of the surface area of the patient, wherein the
heating blanket
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling a patient's body intravascularly and a drug,
said
system comprises a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a mixing-inducing shape comprising
at least
one surface irregularity shaped and arranged to create mixing in surrounding
fluid,
and the surface irregularity comprising a helical ridge and a helical groove,
wherein
said catheter is configured for insertion through the patient's vascular
system of the
patient, and the heat transfer element is configured for (i) placement in the
patient's
vein that drains into the patient's heart, (ii) the circulation of fluid
therethrough and (iii)
the transfer of heat between blood in the vein and the heat transfer element,
and
further comprising the use of a heating blanket to deliver heat to a
substantial portion
of the surface area of the patient, wherein the heating blanket employs a warm-
air
blower and includes air channels for evenly distributing warm air to the
surface area
of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling a patient's body intravascularly, said system
comprising a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a mixing-inducing shape comprising at least
one
surface irregularity shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularity comprising a helical ridge and a helical groove;
wherein said
catheter is configured for insertion through the patient's vascular system,
and the
heat transfer element is configured for (i) placement in the patient's vein
that drains
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into the patient's heart, (ii) the circulation of fluid therethrough and (iii)
the transfer of
heat between blood in the vein and the heat transfer element, and further
comprising
the use of a heating blanket to deliver heat to a substantial portion of the
surface area
of the patient, wherein the heating blanket employs a warm-air blower and
includes
air channels for evenly distributing warm air to the surface area of the
selected
portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
platelet aggregation in a blood vessel in which blood is flowing, said heat
transfer
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a mixing-inducing shape comprising
at least
one surface irregularity shaped and arranged to create mixing in surrounding
fluid,
and the surface irregularity comprising a helical ridge and a helical groove;
wherein
said catheter is configured for insertion through the vascular system of the
patient,
and the heat transfer element is configured for (i) placement in the patient's
blood
vessel in which blood is flowing, (ii) the circulation of fluid therethrough
and (iii) the
transfer of heat between the blood in the vessel and the heat transfer
element,
whereby upon said use the blood is cooled and platelet aggregation is
substantially
reduced, and further comprising the use of a heating blanket to deliver heat
to a
substantial portion of the surface area of the patient, wherein the heating
blanket
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
dependence on drug therapies in treating insults or injuries resulting in
ischemia, said
heat transfer system comprising a catheter having a heat transfer element
attached
to a distal end thereof, the heat transfer element having a mixing-inducing
shape
comprising at least one surface irregularity shaped and arranged to create
mixing in
surrounding fluid, and the surface irregularity comprising a helical ridge and
a helical
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,
64869-1327D
groove; wherein said catheter is configured for insertion through the vascular
system
of the patient, and the heat transfer element is configured for (i) placement
in the
patient's blood vessel in which blood is flowing, (ii) the circulation of
fluid therethrough
and (iii) the transfer of heat between the blood in the vessel and the heat
transfer
element, whereby upon said use the blood is cooled, and further comprising the
use
of a heating blanket to deliver heat to a substantial portion of the surface
area of the
patient, wherein the heating blanket employs a warm-air blower and includes
air
channels for evenly distributing warm air to the surface area of the selected
portion of
the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing cell
damage during and after a myocardial infarction, said heat transfer system
comprising a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a mixing-inducing shape comprising at least
one
surface irregularity shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularity comprises a helical ridge and a helical groove,
wherein said
catheter is configured for insertion through the vascular system of the
patient, and the
heat transfer element is configured for (i) placement in the patient's vein,
said vein
being selected from superior vena cava, inferior vena cava, or a combination
thereof,
(ii) the circulation of fluid therethrough, and (iii) the transfer of heat
between the blood
in the vein and the heat transfer element, whereby upon said use at least one
of
platelet aggregation, oxygen demands, and the metabolic rate of the heart is
reduced
or bradycardia is induced, and further comprising the use of a heating blanket
to
deliver heat to a substantial portion of the surface area of the patient,
wherein the
heating blanket employs a warm-air blower and includes air channels for evenly
distributing warm air to the surface area of the selected portion of the
patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
stenoses recurring following angioplasty, wherein said heat transfer system
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comprises a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a mixing-inducing shape comprising at least
one
surface irregularity shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularity comprising a helical ridge and a helical groove; said
catheter
configured for insertion through the vascular system of the patient, and the
heat
transfer element is configured for (i) placement in the patient's blood
vessel, (ii) the
circulation of fluid therethrough and (iii) the transfer of heat between blood
in the
vessel to the heat transfer element, whereby upon said use the blood and the
blood
vessel are cooled, and further comprising the use of a heating blanket to
deliver heat
to a substantial portion of the surface area of the patient, wherein the
heating blanket
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
reperfusion injury following a reflow operation, wherein said heat transfer
system
comprises a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a mixing-inducing shape comprising at least
one
surface irregularity shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularity comprising a helical ridge and a helical groove;
wherein said
catheter is configured for insertion through the vascular system of the
patient, and the
heat transfer element is configured for (i) placement in a blood vessel in
which blood
is flowing, (ii) the circulation of fluid therethrough, and (iii) the transfer
of heat
between the blood in the vessel and the heat transfer element, whereby upon
said
use the blood vessel is cooled, and further comprising the use of a heating
blanket to
deliver heat to a substantial portion of the surface area of the patient,
wherein the
heating blanket employs a warm-air blower and includes air channels for evenly
distributing warm air to the surface area of the selected portion of the
patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for heating a patient's body intravascularly and a drug,
said
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system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a plurality of heat transfer
segments
connected by flexible joints, the heat transfer segments comprising at least
one
surface irregularity shaped and arranged to create mixing in surrounding
fluid, the
surface irregularity comprising a helical ridge and a helical groove formed on
each
heat transfer segment; and the helical ridge on each heat transfer segment
having an
opposite helical twist to the helical ridges on adjacent heat transfer
segments,
wherein said catheter is configured for insertion through the patient's
vascular
system, and the heat transfer element is configured for (i) placement in the
patient's
vein that drains into the patient's heart, (ii) the circulation of fluid
therethrough and (iii)
the transfer of heat between blood in the vein and the heat transfer element,
and
further comprising the use of a heating blanket to deliver heat to a
substantial portion
of the surface area of the patient, wherein the heating blanket employs a warm-
air
blower and includes air channels for evenly distributing warm air to the
surface area
of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for heating a patient's body intravascularly and a drug,
said
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a mixing-inducing shape comprising
at least
one surface irregularity shaped and arranged to create mixing in surrounding
fluid,
and the surface irregularity comprising a helical ridge and a helical groove,
wherein
said catheter is configured for insertion through the patient's vascular
system of the
patient, and the heat transfer element is configured for (i) placement in the
patient's
vein that drains into the patient's heart, (ii) the circulation of fluid
therethrough and (iii)
the transfer of heat between blood in the vein and the heat transfer element,
and
further comprising the use of a heating blanket to deliver heat to a
substantial portion
of the surface area of the patient, wherein the heating blanket employs a warm-
air
blower and includes air channels for evenly distributing warm air to the
surface area
of the selected portion of the patient's body.
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In another aspect of the present invention, there is provided use of a
heat transfer system for heating a patient's body intravascularly, said system
comprising a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a mixing-inducing shape comprising at least
one
surface irregularity shaped and arranged to create mixing in surrounding
fluid, and
the surface irregularity comprising a helical ridge and a helical groove;
wherein said
catheter is configured for insertion through the patient's vascular system,
and the
heat transfer element is configured for (i) placement in the patient's vein
that drains
into the patient's heart, (ii) the circulation of fluid therethrough and (iii)
the transfer of
heat between blood in the vein and the heat transfer element, and further
comprising
the use of a heating blanket to deliver heat to a substantial portion of the
surface area
of the patient, wherein the heating blanket employs a warm-air blower and
includes
air channels for evenly distributing warm air to the surface area of the
selected
portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling or heating a patient's body intravascularly,
said
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a mixing-inducing shape, wherein
said
catheter is configured for insertion through the patient's vascular system and
the heat
transfer element is configured for (i) placement in a vein that drains into
the patient's
heart, (ii) the circulation of fluid therethrough, and (iii) the transfer of
heat between
blood in the vein and the heat transfer element, and further comprising the
use of a
heating blanket to deliver heat to a substantial portion of the surface area
of the
patient, wherein the heating blanket employs a warm-air blower and includes
air
channels for evenly distributing warm air to the surface area of the selected
portion of
the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
platelet aggregation in a blood vessel in which blood is flowing, said heat
transfer
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system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a mixing-inducing shape, wherein
said
catheter is configured for insertion through the vascular system of the
patient and the
heat transfer element is configured for (i) placement in a blood vessel in
which blood
is flowing, (ii) the circulation of fluid therethrough, and (iii) the transfer
of heat
between the blood in the vessel and the heat transfer element, whereby the
blood is
cooled and platelet aggregation is substantially reduced, and further
comprising the
use of a heating blanket to deliver heat to a substantial portion of the
surface area of
the patient, wherein the heating blanket employs a warm-air blower and
includes air
channels for evenly distributing warm air to the surface area of the selected
portion of
the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
dependence on drug therapies in treating insults or injuries resulting in
ischemia, said
heat transfer system comprising a catheter having a heat transfer element
attached
to a distal end thereof, the heat transfer element having a mixing-inducing
shape,
wherein said catheter is configured for insertion through the vascular system
of the
patient and the heat transfer element is configured for (i) placement in a
blood vessel
in which blood is flowing, (ii) the circulation of fluid therethrough, and
(iii) the transfer
of heat between the blood in the vessel and the heat transfer element, whereby
the
blood is cooled, and further comprising the use of a heating blanket to
deliver heat to
a substantial portion of the surface area of the patient, wherein the heating
blanket
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing cell
damage during and after a myocardial infarction, said heat transfer system
comprising a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a mixing-inducing shape, wherein said
catheter is
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configured for insertion through the vascular system of the patient and the
heat
transfer element is configured for (i) placement in a vein, said vein being
selected
from superior vena cava, inferior vena cava, or both, (ii) the circulation of
fluid
therethrough, and (iii) the transfer of heat between the blood in the vein and
the heat
transfer element, whereby at least one of platelet aggregation, oxygen
demands, and
the metabolic rate of the heart is reduced or bradycardia is induced, and
further
comprising the use of a heating blanket to deliver heat to a substantial
portion of the
surface area of the patient, wherein the heating blanket employs a warm-air
blower
and includes air channels for evenly distributing warm air to the surface area
of the
selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
stenoses recurring following angioplasty, said heat transfer system comprising
a
catheter having a heat transfer element attached to a distal end thereof, the
heat
transfer element having a mixing-inducing shape, wherein said catheter is
configured
for insertion through the vascular system of the patient and the heat transfer
element
is configured for (i) placement in a blood vessel, (ii) the circulation of
fluid
therethrough, and (iii) the transfer of heat between blood in the vessel to
the heat
transfer element, whereby the blood and the blood vessel are cooled, and
further
comprising the use of a heating blanket to deliver heat to a substantial
portion of the
surface area of the patient, wherein the heating blanket employs a warm-air
blower
and includes air channels for evenly distributing warm air to the surface area
of the
selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system in a vascular system of a patient for substantially
reducing
reperfusion injury following a reflow operation, said heat transfer system
comprising a
catheter having a heat transfer element attached to a distal end thereof, the
heat
transfer element having a mixing-inducing shape, wherein said catheter is
configured
for insertion through the vascular system of the patient and the heat transfer
element
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is configured for (i) placement in a blood vessel in which blood is flowing,
(ii) the
circulation of fluid therethrough, and (iii) the transfer of heat between the
blood in the
vessel and the heat transfer element, whereby the blood vessel is cooled, and
further
comprising the use of a heating blanket to deliver heat to a substantial
portion of the
surface area of the patient, wherein the heating blanket employs a warm-air
blower
and includes air channels for evenly distributing warm air to the surface area
of the
selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling or heating a patient's body intravascularly,
said
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a plurality of heat transfer
segments
connected by flexible joints; wherein the catheter is configured for insertion
through
the vascular system of the patient to place the heat transfer element in a
vein that
drains into the heart of the patient; and the heat transfer element is
configured for (i)
the circulation of fluid therethrough and (ii) the transfer of heat between
the blood in
the vein and the heat transfer element, and further comprising the use of a
heating
blanket to deliver heat to a substantial portion of the surface area of the
patient,
wherein the heating blanket employs a warm-air blower and includes air
channels for
evenly distributing warm air to the surface area of the selected portion of
the patient's
body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing platelet aggregation in a
blood vessel
in which blood is flowing, said system comprising a catheter having a heat
transfer
element attached to a distal end thereof, the heat transfer element including
a
plurality of heat transfer segments connected by flexible joints; wherein the
catheter
is configured for insertion through the vascular system of the patient to
place the heat
transfer element in a blood vessel in which blood is flowing; and the heat
transfer
element is configured for (i) the circulation of fluid therethrough; and (ii)
the transfer of
heat from the blood in the vessel to the heat transfer element, whereby blood
is
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cooled and platelet aggregation is substantially reduced, and further
comprising the
use of a heating blanket to deliver heat to a substantial portion of the
surface area of
the patient, wherein the heating blanket employs a warm-air blower and
includes air
channels for evenly distributing warm air to the surface area of the selected
portion of
the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing dependence on drug therapies
in
treating insults or injuries resulting in ischemia, said system comprising a
catheter
having a heat transfer element attached to a distal end thereof, the heat
transfer
element including a plurality of heat transfer segments connected by flexible
joints;
wherein the catheter is configured for insertion through the vascular system
of the
patient to place the heat transfer element in a blood vessel in which blood is
flowing;
and the heat transfer element is configured for (i) the circulation of fluid
therethrough;
and (ii) the transfer of heat from the blood in the vessel to the heat
transfer element,
whereby blood is cooled, and further comprising the use of a heating blanket
to
deliver heat to a substantial portion of the surface area of the patient,
wherein the
heating blanket employs a warm-air blower and includes air channels for evenly
distributing warm air to the surface area of the selected portion of the
patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing cell damage during and after a
myocardial infarction, said system comprising a catheter having a heat
transfer
element attached to a distal end thereof, the heat transfer element including
a
plurality of heat transfer segments connected by flexible joints; wherein the
catheter
is configured for insertion through the vascular system of the patient to
place the heat
transfer element in a vein selected from the group consisting of the superior
vena
cava, the inferior vena cava, and both; and the heat transfer element is
configured for
(i) the circulation of fluid therethrough and (ii) the transfer of heat from
the blood in
the vein to the heat transfer element, whereby at least one of platelet
aggregation,
oxygen demands, and the metabolic rate of the heart is reduced or bradycardia
is
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induced, and further comprising the use of a heating blanket to deliver heat
to a
substantial portion of the surface area of the patient, wherein the heating
blanket
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing stenoses recurring following
angioplasty or a stenting operation on a blood of a patient, said system
comprising a
catheter having a heat transfer element attached to a distal end thereof, the
heat
transfer element including a plurality of heat transfer segments connected by
flexible
joints; wherein the catheter is configured for insertion through the vascular
system of
the patient to place the heat transfer element in the blood vessel; and the
heat
transfer element is configured for (i) the circulation of fluid therethrough
and (ii) the
transfer of heat from the blood in the vessel to the heat transfer element,
whereby
blood and the blood vessel wall is cooled, and further comprising the use of a
heating
blanket to deliver heat to a substantial portion of the surface area of the
patient,
wherein the heating blanket employs a warm-air blower and includes air
channels for
evenly distributing warm air to the surface area of the selected portion of
the patient's
body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing reperfusion injury following
reflow
operation on a blood vessel of a patient, said system comprising: a catheter
having a
heat transfer element attached to a distal end thereof, the heat transfer
element
including a plurality of heat transfer segments connected by flexible joints;
wherein
the catheter is configured for insertion through the vascular system of the
patient to
place the heat transfer element in the blood vessel; and the heat transfer
system is
configured for (i) the circulation of fluid therethrough; and (ii) the
transfer of heat from
the blood in the vessel to the heat transfer element, whereby blood in the
vessel is
cooled, and further comprising the use of a heating blanket to deliver heat to
a
substantial portion of the surface area of the patient, wherein the heating
blanket
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=
64869-1327D
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling or heating a patient's body intravascularly
and a
drug, said system comprising: a catheter having a heat transfer element
attached to
a distal end thereof, the heat transfer element including a plurality of heat
transfer
segments connected by flexible joints; wherein the catheter is configured for
insertion
through the vascular system of the patient to place the heat transfer element
in a vein
that drains into the heart of the patient; and the heat transfer element is
configured for
(i) the circulation of fluid therethrough; and (ii) the transfer of heat
between the blood
in the vein and the heat transfer element, and further comprising the use of a
heating
blanket to deliver heat to a substantial portion of the surface area of the
patient,
wherein the heating blanket employs a warm-air blower and includes air
channels for
evenly distributing warm air to the surface area of the selected portion of
the patient's
body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling or heating a patient's body intravascularly,
said
system comprising a catheter having a heat transfer element attached to a
distal end
thereof, the heat transfer element having a mixing-inducing shape; wherein the
catheter is configured for insertion through the vascular system of the
patient to place
the heat transfer element in a vein that drains into the heart of the patient;
and the
heat transfer element is configured for (i) the circulation of fluid
therethrough; and (ii)
the transfer of heat between the blood in the vein and the heat transfer
element, and
further comprising the use of a heating blanket to deliver heat to a
substantial portion
of the surface area of the patient, wherein the heating blanket employs a warm-
air
blower and includes air channels for evenly distributing warm air to the
surface area
of the selected portion of the patient's body.
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In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing platelet aggregation in a
blood vessel
in which blood is flowing, said system comprising a catheter having a heat
transfer
element attached to a distal end thereof, the heat transfer element having a
mixing-
inducing shape; wherein the catheter is configured for insertion through the
vascular
system of the patient to place the heat transfer element in a blood vessel in
which
blood is flowing; and the heat transfer element is configured for (i) the
circulation of
fluid therethrough; and (ii) the transfer of heat from the blood in the vessel
to the heat
transfer element, whereby blood is cooled and platelet aggregation is
substantially
reduced, and further comprising the use of a heating blanket to deliver heat
to a
substantial portion of the surface area of the patient, wherein the heating
blanket
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing dependence on drug therapies
in
treating insults or injuries resulting in ischemia, said system comprising a
catheter
having a heat transfer element attached to a distal end thereof, the heat
transfer
element having a mixing-inducing shape; wherein the catheter is configured for
insertion through the vascular system of the patient to place the heat
transfer element
in a blood vessel in which blood is flowing; and the heat transfer element is
configured for (i) the circulation of fluid therethrough; and (ii) the
transfer of heat from
the blood in the vessel to the heat transfer element, whereby blood is cooled,
and
further comprising the use of a heating blanket to deliver heat to a
substantial portion
of the surface area of the patient, wherein the heating blanket employs a warm-
air
blower and includes air channels for evenly distributing warm air to the
surface area
of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing cell damage during and after a
myocardial infarction, said system comprising a catheter having a heat
transfer
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element attached to a distal end thereof, the heat transfer element having a
mixing-
inducing shape; wherein the catheter is configured for insertion through the
vascular
system of the patient to place the heat transfer element in a vein selected
from the
group consisting of the superior vena cava, the inferior vena cava, and both;
and the
heat transfer element is configured for (i) the circulation of fluid
therethrough; and (ii)
the transfer of heat from the blood in the vein to the heat transfer element,
whereby at
least one of platelet aggregation, oxygen demands, and the metabolic rate of
the
heart is reduced or bradycardia is induced, and further comprising the use of
a
heating blanket to deliver heat to a substantial portion of the surface area
of the
patient, wherein the heating blanket employs a warm-air blower and includes
air
channels for evenly distributing warm air to the surface area of the selected
portion of
the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing stenoses recurring following
angioplasty or stenting operation on a blood vessel of a patient, said system
comprising a catheter having a heat transfer element attached to a distal end
thereof,
the heat transfer element having a mixing-inducing shape; wherein the catheter
is
configured for insertion through the vascular system of the patient to place
the heat
transfer element in the blood vessel; and the heat transfer element is
configured for
(i) the circulation of fluid therethrough; and (ii) the transfer of heat from
the blood in
the vessel to the heat transfer element, whereby blood and the blood vessel
wall is
cooled, and further comprising the use of a heating blanket to deliver heat to
a
substantial portion of the surface area of the patient, wherein the heating
blanket
employs a warm-air blower and includes air channels for evenly distributing
warm air
to the surface area of the selected portion of the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for substantially reducing reperfusion injury following
reflow
operation on a blood vessel of a patient, said system comprising a catheter
having a
heat transfer element attached to a distal end thereof, the heat transfer
element
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having a mixing-inducing shape; wherein the catheter is configured for
insertion
through the vascular system of the patient to place the heat transfer element
in the
blood vessel; and the heat transfer element is configured for (i) the
circulation of fluid
therethrough; and (ii) the transfer of heat from the blood in the vessel to
the heat
transfer element, whereby blood in the vessel is cooled, and further
comprising the
use of a heating blanket to deliver heat to a substantial portion of the
surface area of
the patient, wherein the heating blanket employs a warm-air blower and
includes air
channels for evenly distributing warm air to the surface area of the selected
portion of
the patient's body.
In another aspect of the present invention, there is provided use of a
heat transfer system for cooling or heating a patient's body intravascularly
and a
thermoregulatory drug, said system comprising a catheter having a heat
transfer
element attached to a distal end thereof, the heat transfer element having a
mixing-
inducing shape; wherein the catheter is configured for insertion through the
vascular
system of the patient to place the heat transfer element in a vein that drains
into the
heart of the patient; and the heat transfer element is configured for (i) the
circulation
of fluid therethrough; and (ii) the transfer of heat between the blood in the
vein and
the heat transfer element, and further comprising the use of a heating blanket
to
deliver heat to a substantial portion of the surface area of the patient,
wherein the
heating blanket employs a warm-air blower and includes air channels for evenly
distributing warm air to the surface area of the selected portion of the
patient's body.
Other uses of the heat transfer system also include: reducing platelet
aggregation in a blood vessel in which blood is flowing; reducing dependence
on
drug therapies in treating insults or injuries resulting in ischemia; reducing
stenoses
recurring following angioplasty; reducing reperfusion injury following a
reflow
operation on a blood vessel of a patient; reducing cell damage during and
after a
myocardial infarction; and heating a patient's body intravascularly. The use
may
further include a drug, such as a thermoregulatory drug.
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BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
Figure 1 is an elevation view of one embodiment of a heat transfer
element according to the invention;
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CA 02524524 2000-07-28
,
Figure 2 is a longitudinal section view of the heat transfer element of Figure
1;
Figure 3 is a transverse section view of the heat transfer element of Figure
1;
Figure 4 is a perspective view of the heat transfer element of Figure 1 in use
within a blood vessel;
5 Figure 5 is a cut-away perspective view of an alternative embodiment
of a heat
transfer element according to the invention;
Figure 6 is a transverse section view of the heat transfer element of Figure
5;
Figure 7 is a schematic representation of the heat transfer element being used
in
one embodiment to provide hypothermia to a patient by causing total body
cooling and
10 then rewarming the body;
Figure 8 is a schematic representation of the heat transfer element being used
in
another embodiment to provide hypothermia to a patient by causing total body
cooling
and then rewarrning the body;
Figure 9 is a schematic representation of the heat transfer element being used
in
15 an embodiment within the superior vena cava;
Figure 10 is a graph showing preferential cooling of the high flow organs of
the
body under a hypothermic therapy; and
Figure 11 is a flowchart showing an exemplary method of the invention
employing heating blankets and thermoregulatory drugs.
DETAILED DESCRIPTION OF THE INVENTION
OVERVIEW
A one or two-step process and a one or two-piece device may be employed to
intravascularly lower the temperature of a body in order to induce therapeutic
hypothermia. A cooling element may be placed in a high-flow vein such as the
vena
cavae to absorb heat from the blood flowing into the heart. This transfer of
heat causes a
cooling of the blood flowing through the heart and thus throughout the
vasculature. Such
a method and device may therapeutically be used to induce an artificial state
of
hypothermia.
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A heat transfer element that systemically cools blood should be capable of
providing the necessary heat transfer rate to produce the desired cooling
effect throughout
the vasculature. This may be up to or greater than 300 watts, and is at least
partially
dependent on the mass of the patient and the rate of blood flow. Surface
features may be
employed on the heat transfer element to enhance the heat transfer rate. The
surface
features and other components of the heat transfer element are described in
more detail
below.
One problem with hypothermia as a therapy is that the patient's
thermoregulatory
defenses initiate, attempting to defeat the hypothermia. Methods and devices
may be
used to lessen the thermoregulatory response. For example, a heating blanket
may cover
the patient. In this way, the patient may be made more comfortable.
Thermoregulatory
drugs may also be employed to lower the trigger point at which the patient's
thermoregulatory system begins to initiate defenses. Such drugs are described
in more
detail below. A method employing thermoregulatory drugs, heating blankets, and
heat
transfer elements is also disclosed below.
ANATOMICAL PLACEMENT
The internal jugular vein is the vein that directly drains the brain. The
external
jugular joins the internal jugular at the base of the neck. The internal
jugular veins join
the subclavian veins to form the brachiocephalic veins that in turn drain into
the superior
vena cava. The superior vena cava drains into the right atrium of the heart as
may be seen
by referring ahead to Fig. 9. The superior vena cava supplies blood to the
heart from the
upper part of the body.
A cooling element may be placed into the superior vena cava, inferior vena
cava,
or otherwise into a vein which feeds into the superior vena cava or otherwise
into the
heart to cool the body. A physician percutaneously places the catheter into
the subclavian
or internal or external jugular veins to access the superior vena cava. The
blood, cooled
by the heat transfer element, may be processed by the heart and provided to
the body in
oxygenated form to be used as a conductive medium to cool the body. The lungs
have a
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CA 02524524 2000-07-28
fairly low heat capacity, and thus the lungs do not cause appreciable
rewarming of the
flowing blood.
The vasculature by its very nature provides preferential blood flow to the
high
blood flow organs such as the brain and the heart. Thus, these organs are
preferentially
cooled by such a procedure as is also shown experimentally in Figure 10.
Figure 10 is a
graph of measured temperature plotted versus cooling time. This graph show the
effect
of placing a cooling element in the superior vena cavae of a sheep. The core
body
temperature as measured by an esophageal probe is shown by curve 82. The brain
temperature is shown by curve 86. The brain temperature is seen to decrease
more
rapidly than the core body temperature throughout the experiment. The
inventors believe
this effect to be due to the preferential supply of blood provided to the
brain and heart.
This effect may be even more pronounced if thermoregulatory effects, such as
vasoconstriction, occur that tend to focus blood supply to the core vascular
system and
away from the peripheral vascular system.
HEAT TRANSFER
When a heat transfer element is inserted approximately coaxially into an
artery or
vein, the primary mechanism of heat transfer between the surface of the heat
transfer
element and the blood is forced convection. Convection relies upon the
movement of
fluid to transfer heat. Forced convection results when an external force
causes motion
within the fluid. In the case of arterial or venous flow, the beating heart
causes the
motion of the blood around the heat transfer element.
The magnitude of the heat transfer rate is proportional to the surface area of
the
heat transfer element, the temperature differential, and the heat transfer
coefficient of the
heat transfer element.
The receiving artery or vein into which the heat transfer element is placed
has a
limited diameter and length. Thus, the surface area of the heat transfer
element must be
limited to avoid significant obstruction of the artery or vein and to allow
the heat transfer
element to easily pass through the vascular system. For placement within the
superior
vena cava via the external jugular, the cross sectional diameter of the heat
transfer
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CA 02524524 2000-07-28
element may be limited to about 5-6 mm, and its length may be limited to
approximately
10-15 cm. For placement within the inferior vena cava, the cross sectional
diameter of
the heat transfer element may be limited to about 6-7 mm, and its length may
be limited
to approximately 25-35 cm.
Decreasing the surface temperature of the heat transfer element can increase
the
temperature differential. However, the minimum allowable surface temperature
is limited
by the characteristics of blood. Blood freezes at approximately 0 C. When the
blood
approaches freezing, ice emboli may form in the blood, which may lodge
downstream,
causing serious ischemic injury. Furthermore, reducing the temperature of the
blood also
increases its viscosity, which results in a small decrease in the value of the
convection
heat transfer coefficient. In addition, increased viscosity of the blood may
result in an
increase in the pressure drop within the artery, thus compromising the flow of
blood to
the brain. Given the above constraints, it is advantageous to limit the
minimum allowable
surface temperature of the cooling element to approximately 5 C. This results
in a
maximum temperature differential between the blood stream and the cooling
element of
approximately 32 C. For other physiological reasons, there are limits on the
maximum
allowable surface temperature of the warming element.
The mechanisms by which the value of the convection heat transfer coefficient
may be increased are complex. However, it is well known that the convection
heat
transfer coefficient increases with the level of "mixing" or "turbulent"
kinetic energy in
the fluid flow. Thus it is advantageous to have blood flow with a high degree
of mixing
in contact with the heat transfer element.
The blood flow has a considerably more stable flux in the superior vena cava
than
in an artery. However, the blood flow in the superior vena cava still has a
high degree of
inherent mixing or turbulence. Reynolds numbers in the superior vena cava may
range,
for example, from 2,000 to 5,000. Thus, blood cooling in the superior vena
cava may
benefit from enhancing the level of mixing with the heat transfer element but
this benefit
may be substantially less than that caused by the inherent mixing.
10
CA 02524524 2000-07-28
BOUNDARY LAYERS
A thin boundary layer has been shown to form during the cardiac cycle.
Boundary layers develop adjacent to the heat transfer element as well as next
to the walls
of the artery or vein. Each of these boundary layers has approximately the
same
thickness as the boundary layer that would have developed at the wall of the
artery in the
absence of the heat transfer element. The free stream flow region is developed
in an
annular ring around the heat transfer element. The heat transfer element used
in such a
vessel should reduce the formation of such viscous boundary layers.
HEAT TRANSFER ELEMENT CHARACTERISTICS AND DESCRIPTION
The intravascular heat transfer element should be flexible in order to be
placed
within the vena cavae or other veins or arteries. The flexibility of the heat
transfer
element is an important characteristic because the same is typically inserted
into a vein
such as the external jugular and accesses the superior vena cava by initially
passing
though a series of one or more branches. Further, the heat transfer element is
ideally
constructed from a highly thermally conductive material such as metal in order
to
facilitate heat transfer. The use of a highly thermally conductive material
increases the
heat transfer rate for a given temperature differential between the working
fluid within the
heat transfer element and the blood. This facilitates the use of a higher
temperature
coolant, or lower temperature warming fluid, within the heat transfer element,
allowing
safer working fluids, such as water or saline, to be used. Highly thermally
conductive
materials, such as metals, tend to be rigid. Therefore, the design of the heat
transfer
element should facilitate flexibility in an inherently inflexible material.
It is estimated that the cooling element should absorb at least about 300
Watts of
heat when placed in the superior vena cava to lower the temperature of the
body to
between about 30 C and 34 C. These temperatures are thought to be appropriate
to
obtain the benefits of hypothermia described above. The power removed
determines how
quickly the target temperature can be reached. For example, in a stroke
therapy in which
it is desired to lower brain temperature, the same may be lowered about 4 C
per hour in a
70 kg human upon removal of 300 Watts.
11
CA 02524524 2015-02-12
One embodiment of the invention uses a modular design. This design creates
helical blood flow and produces a level of mixing in the blood flow by
periodically
forcing abrupt changes in the direction of the helical blood flow. The abrupt
changes in
flow direction are achieved through the use of a series of two or more heat
transfer
segments, each included of one or more helical ridges. The use of periodic
abrupt
changes in the helical direction of the blood flow in order to induce strong
free stream
turbulence may be illustrated with reference to a common clothes washing
machine. The
rotor of a washing machine spins initially in one direction causing laminar
flow. When
the rotor abruptly reverses direction, significant turbulent kinetic energy is
created within
the entire wash basin as the changing currents cause random turbulent motion
within the
clothes-water slurry. These surface features also tend to increase the surface
area of the
heat transfer element, further enhancing heat transfer.
Figure 1 is an elevation view of one embodiment of a cooling element 14
according to the present invention. The heat transfer element 14 includes a
series of
elongated, articulated segments or modules 20, 22, 24. Three such segments are
shown in
this embodiment, but two or more such segments could be used.
As seen in Figure 1, a first elongated heat transfer segment 20
is located at the proximal end of the heat transfer element 14. A mixing-
inducing exterior
surface of the segment 20 includes four parallel helical ridges 28 with four
parallel helical
grooves 26 therebetween. One, two, three, or more parallel helical ridges 28
could also
be used. In this
embodiment,
the helical ridges 28 and the helical grooves 26 of the heat transfer segment
20 have a left
hand twist, referred to herein as a counter-clockwise spiral or helical
rotation, as they
proceed toward the distal end of the heat transfer segment 20.
The first heat transfer segment 20 is coupled to a second elongated heat
transfer
segment 22 by a first bellows section 25, which provides flexibility and
compressibility.
The second heat transfer segment 22 includes one or more helical ridges 32
with one or
more helical grooves 30 therebetween. The ridges 32 and grooves 30 have a
right hand,
or clockwise, twist as they proceed toward the distal end of the heat transfer
segment 22.
The second heat transfer segment 22 is coupled to a third elongated heat
transfer segment
12
CA 02524524 2000-07-28
= 24 by a second bellows section 27. The third heat transfer segment 24
includes one or
more helical ridges 36 with one or more helical grooves 34 therebetween. The
helical
ridge 36 and the helical groove 34 have a left hand, or counter-clockwise,
twist as they
proceed toward the distal end of the heat transfer segment 24. Thus,
successive heat
transfer segments 20, 22, 24 of the heat transfer element 14 alternate between
having
clockwise and counterclockwise helical twists. The actual left or right hand
twist of any
particular segment is immaterial, as long as adjacent segments have opposite
helical
twist.
In addition, the rounded contours of the ridges 28, 32, 36 allow the heat
transfer
element 14 to maintain a relatively atraumatic profile, thereby minimizing the
possibility
of damage to the blood vessel wall. A heat transfer element according to the
present
invention may include two, three, or more heat transfer segments.
The bellows sections 25, 27 are formed from seamless and nonporous materials,
such as metal, and therefore are impermeable to gas, which can be particularly
important,
depending on the type of working fluid that is cycled through the heat
transfer element
14. The structure of the bellows sections 25, 27 allows them to bend, extend
and
compress, which increases the flexibility of the heat transfer element 14 so
that it is more
readily able to navigate through blood vessels. The bellows sections 25, 27
also provide
for axial compression of the heat transfer element 14, which can limit the
trauma when
the distal end of the heat transfer element 14 abuts a blood vessel wall. The
bellows
sections 25, 27 are also able to tolerate cryogenic temperatures without a
loss of
performance. In alternative embodiments, the bellows may be replaced by
flexible
polymer tubes, which are bonded between adjacent heat transfer segments.
The exterior surfaces of the heat transfer element 14 can be made from metal,
and
may include very high thermal conductivity materials such as nickel, thereby
facilitating
heat transfer. Alternatively, other metals such as stainless steel, titanium,
aluminum,
silver, copper and the like, can be used, with or without an appropriate
coating or
treatment to enhance biocompatibility or inhibit clot formation. Suitable
biocompatible
coatings include, e.g., gold, platinum or polymer paralyene. The heat transfer
element 14
may be manufactured by plating a thin layer of metal on a mandrel that has the
13
CA 02524524 2000-07-28
appropriate pattern. In this way, the heat transfer element 14 may be
manufactured
inexpensively in large quantities, which is an important feature in a
disposable medical
device.
Because the heat transfer element 14 may dwell within .the blood vessel for
extended periods of time, such as 24-48 hours or even longer, it may be
desirable to treat
the surfaces of the heat transfer element 14 to avoid clot formation. In
particular, one
may wish to treat the bellows sections 25, 27 because stagnation of the blood
flow may
occur in the convolutions, thus allowing clots to form and cling to the
surface to form a
thrombus. One means by which to prevent thrombus formation is to bind an
antithrombogenic agent to the surface of the heat transfer element 14. For
example,
heparin is known to inhibit clot formation and is also known to be useful as a
biocoating.
Alternatively, the surfaces of the heat transfer element 14 may be bombarded
with ions
such as nitrogen. Bombardment with nitrogen can harden and smooth the surface
and
thus prevent adherence of clotting factors. Another coating that provides
beneficial
properties may be a lubricious coating. Lubricious coatings, on both the heat
transfer
element and its associated catheter, allow for easier placement in the, e.g.,
vena cava.
Figure 2 is a longitudinal sectional view of the heat transfer element 14 of
an
embodiment of the invention, taken along line 2-2 in Figure 1. Some interior
contours
are omitted for purposes of clarity. An inner tube 42 creates an inner lumen
40 and an
outer lumen 46 within the heat transfer element 14. Once the heat transfer
element 14 is
in place in the blood vessel, a working fluid such as saline or other aqueous
solution may
be circulated through the heat transfer element 14. Fluid flows up a supply
catheter into
the inner lumen 40. At the distal end of the heat transfer element 14, the
working fluid
exits the inner lumen 40 and enters the outer lumen 46. As the working fluid
flows
through the outer lumen 46, heat is transferred from the working fluid to the
exterior
surface 37 of the heat transfer element 14. Because the heat transfer element
14 is
constructed from a high conductivity material, the temperature of its exterior
surface 37
may reach very close to the temperature of the working fluid. The tube 42 may
be
formed as an insulating divider to thermally separate the inner lumen 40 from
the outer
lumen 46. For example, insulation may be achieved by creating longitudinal air
channels
14
CA 02524524 2000-07-28
in the wall of the insulating tube 42. Alternatively, the insulating tube 42
may be
constructed of a non-thermally conductive material like
polytetrafluoroethylene or
another polymer.
It is important to note that the same mechanisms that govern the heat transfer
rate
between the exterior surface 37 of the heat transfer element 14 and the blood
also govern
the heat transfer rate between the working fluid and the interior surface 38
of the heat
transfer element 14. The heat transfer characteristics of the interior surface
38 are
particularly important when using water, saline or other fluid that remains a
liquid as the
working fluid. Other coolants such as Freon undergo nucleate boiling and
create mixing
through a different mechanism. Saline is a safe working fluid, because it is
non-toxic,
and leakage of saline does not result in a gas embolism, which could occur
with the use of
boiling refrigerants. Since mixing in the working fluid is enhanced by the
shape of the
interior surface 38 of the heat transfer element 14, the working fluid can be
delivered to
the cooling element 14 at a warmer temperature and still achieve the necessary
cooling
rate. Similarly, since mixing in the working fluid is enhanced by the shape of
the interior
surface of the heat transfer element, the working fluid can be delivered to
the warming
element 14 at a cooler temperature and still achieve the necessary warming
rate.
This has a number of beneficial implications in the need for insulation along
the
catheter shaft length. Due to the decreased need for insulation, the catheter
shaft diameter
can be made smaller. The enhanced heat transfer characteristics of the
interior surface of
the heat transfer element 14 also allow the working fluid to be delivered to
the heat
transfer element 14 at lower flow rates and lower pressures. High pressures
may make
the heat transfer element stiff and cause it to push against the wall of the
blood vessel,
thereby shielding part of the exterior surface 37 of the heat transfer element
14 from the
blood. Because of the increased heat transfer characteristics achieved by the
alternating
helical ridges 28, 32, 36, the pressure of the working fluid may be as low as
5
atmospheres, 3 atmospheres, 2 atmospheres or even less than 1 atmosphere.
Figure 3 is a transverse sectional view of the heat transfer element 14 of the
invention, taken at a location denoted by the line 3-3 in Figure 1. Figure 3
illustrates a
five-lobed embodiment, whereas Figure 1 illustrates a four-lobed embodiment.
As
CA 02524524 2000-07-28
mentioned earlier, any number of lobes might be used. In Figure 3, the
construction of
the heat transfer element 14 is clearly shown. The inner lumen 40 is defined
by the
insulating tube 42. The outer lumen 46 is defined by the exterior surface of
the insulating
tube 42 and the interior surface 38 of the heat transfer element 14. In
addition, the helical
ridges 32 and helical grooves 30 may be seen in Figure 3. Although Figure 3
shows four
ridges and four grooves, the number of ridges and grooves may vary. Thus, heat
transfer
elements with 1, 2, 3, 4, 5, 6, 7, 8 or more ridges are specifically
contemplated.
Figure 4 is a perspective view of a heat transfer element 14 in use within a
blood
vessel, showing only one helical lobe per segment for purposes of clarity.
Beginning
from the proximal end of the heat transfer element (not shown in Figure 4), as
the blood
moves forward, the first helical heat transfer segment 20 induces a counter-
clockwise
rotational inertia to the blood. As the blood reaches the second segment 22,
the rotational
direction of the inertia is reversed, causing mixing within the blood.
Further, as the blood
reaches the third segment 24, the rotational direction of the inertia is again
reversed. The
sudden changes in flow direction actively reorient and randomize the velocity
vectors,
thus ensuring mixing throughout the bloodstream. During such mixing, the
velocity
vectors of the blood become more random and, in some cases, become
perpendicular to
the axis of the vessel. Thus, a large portion of the volume of warm blood in
the vessel is
actively brought in contact with the heat transfer element 14, where it can be
cooled by
direct contact rather than being cooled largely by conduction through adjacent
laminar
layers of blood.
Referring back to Figure 1, the heat transfer element 14 has been designed to
address all of the design criteria discussed above. First, the heat transfer
element 14 is
flexible and is made of a highly conductive material. The flexibility is
provided by a
segmental distribution of bellows sections 25, 27 that provide an articulating
mechanism.
Bellows have a known convoluted design that provide flexibility. Second, the
exterior
surface area 37 has been increased through the use of helical ridges 28, 32,
36 and helical
grooves 26, 30, 34. The ridges also allow the heat transfer element 14 to
maintain a
relatively atraumatic profile, thereby minimizing the possibility of damage to
the vessel
wall. Third, the heat transfer element 14 has been designed to promote mixing
both
16
CA 02524524 2000-07-28
internally and externally. The modular or segmental design allows the
direction of the
grooves to be reversed between segments. The alternating helical rotations
create an
alternating flow that results in mixing the blood in a manner analogous to the
mixing
action created by the rotor of a washing machine that switches directions back
and forth.
This action is intended to promote mixing to enhance the heat transfer rate.
The
alternating helical design also causes beneficial mixing, or turbulent kinetic
energy, of the
working fluid flowing internally.
Figure 5 is a cut-away perspective view of an alternative embodiment of a heat
transfer element 50. An external surface 52 of the heat transfer element 50 is
covered
with a series of axially staggered protrusions 54. The staggered nature of the
outer
protrusions 54 is readily seen with reference to Figure 6 which is a
transverse cross-
sectional view taken at a location denoted by the line 6-6 in Figure 5. As the
blood flows
along the external surface 52, it collides with one of the staggered
protrusions 54 and a
turbulent wake flow is created behind the protrusion. As the blood divides and
swirls
alongside of the first staggered protrusion 54, its turbulent wake encounters
another
staggered protrusion 54 within its path preventing the re-lamination of the
flow and
creating yet more mixing. In this way, the velocity vectors are randomized and
mixing is
created not only in the boundary layer but also throughout a large portion of
the free
stream. As is the case with the preferred embodiment, this geometry also
induces a
mixing effect on the internal working fluid flow.
A working fluid is circulated up through an inner lumen 56 defined by an
insulating tube 58 to a distal tip of the heat transfer element 50. The
working fluid then.
traverses an outer lumen 60 in order to transfer heat to the exterior surface
52 of the heat.
transfer element 50. The inside surface of the heat transfer element 50 is
similar to the
exterior surface 52 in order to induce turbulent flow of the working fluid.
The inner
protrusions can be aligned with the outer protrusions 54 as shown in Figure 6
or they can
be offset from the outer protrusions 54 as shown in Figure 5.
17
CA 02524524 2000-07-28
METHOD OF USE
Figure 7 is a schematic representation of the invention being used to cool the
body
of a patient and to warm a portion of the body. The hypothermia apparatus
shown in
Figure 7 includes a first working fluid supply 10, preferably supplying a
chilled liquid
such as water, alcohol or a halogenated hydrocarbon, a first supply catheter
12 and the
cooling element 14. The first supply catheter 12 may have a substantially
coaxial
construction. An inner lumen within the first supply catheter 12 receives
coolant from
the first working fluid supply 10. The coolant travels the length of the first
supply
catheter 12 to the cooling element 14 which serves as the cooling tip of the
catheter. At
the distal end of the cooling element 14, the coolant exits the insulated
interior lumen and
traverses the length of the cooling element 14 in order to decrease the
temperature of the
cooling element 14. The coolant then traverses an outer lumen of the first
supply catheter
12 so that it may be disposed of or recirculated. The first supply catheter 12
is a flexible
catheter having a diameter sufficiently small to allow its distal end to be
inserted
percutaneously into an accessible vein such as the external jugular vein of a
patient as
shown in Figure 7. The first supply catheter 12 is sufficiently long to allow
the cooling
element 14 at the distal end of the first supply catheter 12 to be passed
through the
vascular system of the patient and placed in the superior vena cava 62,
inferior vena cava
(not shown), or other such vein.
The method of inserting the catheter into the patient and routing the cooling
element 14 into a selected vein is well known in the art. Percutaneous
placement of the
heat transfer element 14 into the jugular vein is accomplished directly, since
the jugular
vein is close to the surface. The catheter would reside in the internal
jugular and into the
superior vena cava or even the right atrium.
Although the working fluid supply 10 is shown as an exemplary cooling device,
other devices and working fluids may be used. For example, in order to provide
cooling,
freon, perflourocarbon, water, or saline may be used, as well as other such
coolants.
The cooling element can absorb up to or more than 300 Watts of heat from the
blood stream, resulting in absorption of as much as 100 Watts, 150 Watts, 170
Watts or
more from the brain.
18
CA 02524524 2000-07-28
HEATING BLANKETS
Figure 7 also shows a heating element 66:shown as a heating blanket. Heating
blankets 66 generally are equipped with forced warm-air blowers that blow
heated air
through vents in the blanket in a direction towards the patient. This type of
heating
occurs through the surface area of the skin of the patient, and is partially
dependent on the
surface area extent of the patient. As shown in Figure 7, the heating blanket
66 may
cover most of the patient to warm and provide comfort to the patient. The
heating
blanket 66 need not cover the face and head of the patient in order that the
patient may
more easily breathe.
The heating blanket 66 serves several purposes. By warming the patient,
vasoconstriction is avoided. The patient is also made more comfortable. For
example, it
is commonly agreed that for every- one .degree of core body temperature
reduction, the
patient will continue to feel comfortable if the same experiences a rise in
surface area
(skin) temperature of five degrees. Spasms due to total body hypothermia may
be
avoided. Temperature control of the patient may be more conveniently performed
as the
physician has another variable (the amount of heating) which may be adjusted.
The practice of the present invention is illustrated in the following non-
limiting
example.
Exemplary Procedure
1. The patient is initially assessed, resuscitated, and stabilized.
2. The procedure may be carried out in an angiography suite or surgical suite
equipped
with fluoroscopy.
3. An ultrasound or angiogram of the superior vena cava and external jugular
can be used
to determine the vessel diameter and the blood flow; a catheter with an
appropriately
sized heat transfer element can be selected.
19
CA 02524524 2000-07-28
5. After assessment of the veins, the patient is sterilely prepped and
infiltrated with
lidocaine at a region where the femoral artery may be accessed.
6. The external jugular is cannulated and a guide wire may be inserted to the
superior
vena cava. Placement of the guide wire is confirmed with fluoroscopy.
7. An angiographic catheter can be fed over the wire and contrast media
injected into the
vein to further to assess the anatomy if desired.
8. Alternatively, the external jugular is cannulated and a 10-12.5 french (f)
introducer
sheath is placed.
9. A guide catheter is placed into the superior vena cava. If a guide catheter
is placed, it
can be used to deliver contrast media directly to further assess anatomy.
10. The cooling catheter is placed into the superior vena cava via the guiding
catheter or
over the guidewire.
11. Placement is confirmed if desired with fluoroscopy.
12. Alternatively, the cooling catheter shaft has sufficient pushability and
torqueability
to be placed in the superior vena cava without the aid of a guide wire or
guide catheter.
13. The cooling catheter is connected to a pump circuit also filled with
saline and free
from air bubbles. The pump circuit has a heat exchange section that is
immersed into a
water bath and tubing that is connected to a peristaltic pump. The water bath
is chilled to
approximately 0 C.
14. Cooling is initiated by starting the pump mechanism. The saline within the
cooling
catheter is circulated at 5 cc/sec. The saline travels through the heat
exchanger in the
chilled water bath and is cooled to approximately 1 C.
15. The saline subsequently enters the cooling catheter where it is delivered
to the heat
transfer element. The saline is warmed to approximately 5-7 C as it travels
along the
inner lumen of the catheter shaft to the end of the heat transfer element.
16. The saline then flows back through the heat transfer element in contact
with the
inner metallic surface. The saline is further warmed in the heat transfer
element to 12-15
C, and in the process, heat is absorbed from the blood, cooling the blood to
30 C to 35 C.
During this time, the patient may be warmed with an external heat source such
as a
heating blanket.
CA 02524524 2000-07-28
17. The chilled blood then goes on to chill the body. It is estimated that
less than an
hour will be required to cool the brain to 30 C to 35 C.
18. The warmed saline travels back the outer lumen of the catheter shaft
and is returned
to the chilled water bath where the same is cooled to 1 C.
19. The pressure drops along the length of the circuit are estimated to be
between 1 and
atmospheres.
20. The cooling can be adjusted by increasing or decreasing the flow rate of
the saline.
Monitoring of the temperature drop of the saline along the heat transfer
element will
allow the flow to be adjusted to maintain the desired cooling effect.
10 21. The catheter is left in place to provide cooling for, e.g., 6-48
hours.
Referring to Figure 8, an alternative embodiment is shown in which the heat
transfer element 14 is disposed in the superior vena cava 62 from the axillary
vein rather
than from the external jugular. It is envisioned that the following veins may
be
appropriate to percutaneously insert the heat transfer element: femoral,
internal jugular,
subclavian, and other veins of similar size and position. It is also
envisioned that the
following veins may be appropriate in which to dispose the heat transfer
element during
use: inferior vena cava, superior vena cava, femoral, internal jugular, and
other veins of
similar size and position.
Figure 9 shows a cross-section of the heart in which the heat transfer element
14
is disposed in the superior vena cava 62. The heat transfer element 14 has
rotating helical
grooves 22 as well as counter-rotating helical grooves 24. Between the
rotating and the
counter-rotating grooves are bellows 27. It is believed that a design of this
nature would
enhance the Nusselt number for the flow in the superior vena cava by about 5
to 80.
THERMOREGULATORY DRUGS
The above description discloses mechanical methods of rewarming a patient, or
portions of a patient, to minimize the deleterious consequences of total body
hypothermia. Another procedure which may be performed, either contemporaneous
with
or in place of mechanical warming, is the administration of anti-
vasoconstriction and
21
CA 02524524 2000-07-28
anti-shivering drugs. Such drugs minimize the effect of vasoconstriction which
may
otherwise hinder heat transfer and thus cooling of the patient. In general,
hypothermia
tends to trigger aggressive thermoregulatory defenses in the human body. Such
drugs
also prohibit responses such as shivering which may cause damage to cardiac-
compromised patients by increasing their metabolic rate to dangerous levels.
To limit the effectiveness of thermoregulatory defenses during therapeutic
hypothermia, drugs that induce thermoregulatory tolerance may be employed. A
variety
= of these drugs have been discovered. For example, clonidine, meperidine,
a combination
of clonidine and meperidine, propofol, magnesium, dexmedetomidine, and other
such
drugs may be employed.
It is known that certain drugs inhibit therrnoregulation roughly in proportion
to
their anesthetic properties. Thus, volatile anesthetics (isoflurane,
desflurane, etc.),
propofol, etc. are more effective at inhibiting thermoregulation than opioids
which are in
turn more effective than midazolam and the central alpha agonists. It is
believed that the
combination drug of clonidine and meperidine synergistically reduces
vasoconstriction
and shivering thresholds, synergistically reduces the gain and maximum
intensity of
vasoconstriction and shivering, and produces sufficient inhibition of
thermoregulatory
activity to permit central catheter-based cooling to 32 C without excessive
hypotension,
autonomic nervous system activation, or sedation and respiratory compromise.
These drugs may be particularly important given the rapid onset of
thermoregulatory defenses. For example, vasoconstriction may set in at
temperatures of
only Y2 degree below normal body temperature. Shivering sets in only a
fraction of a
degree below vasoconstriction.
The temperature to which the blood is lowered may be such that
thermoregulatory
responses are not triggered. For example, thermoregulatory responses may be
triggered
at a temperature of 1 ¨ 1 1/2 degrees below normal temperature. Thus, if
normal body
temperature is 37 C, thermoregulatory responses may set in at 35 C.
Thermoregulatory
drugs may used to lower the temperature of the thermoregulatory trigger
threshold to 33
C. Use of the heating blankets described above may allow even further cooling
of the
patient. For example, to lower the patient's temperature from 33 C to 31 C, a
2 C
22
CA 02524524 2000-07-28
= temperature difference, a 2 times 5 C or 10 C rise is surface temperature
may be
employed on the skin of the patient to allow the patient to not "feel" the
extra 2 C
cooling.
A method which combines the thermoregulatory drug methodology and the
heating blanket methodology is described with respect to Figure 11. This
figure is purely
exemplary. Patients' normal body temperatures vary, as do their
thermoregulatory
thresholds.
As shown in Figure 11, the patient may start with a normal body temperature of
37 C and a typical thermoregulatory threshold of 35 C (step 102). In other
words, at
35 C, the patient would begin to shiver and vasoconstrict. A thermoregulatory
drug may
be delivered (step 104) to suppress the thermoregulatory response, changing
the threshold
temperature to, e.g., 35 C. This new value is shown in step 106. The heat
transfer
element may then be placed in a high flow vein, such as the superior or
inferior vena
cavae or both (step 108). Cooling may occur to lower the temperature of the
blood (step
110). The cooling may be in a fashion described in more detail above. The
cooling
results in the patient undergoing hypothermia and achieving a hypothermic
temperature
of, e.g., 33 C (step 112). More cooling may be performed at this stage, but as
the
thermoregulatory threshold has only been suppressed to 33 C (step 112),
shivering and
vasoconstriction would deleteriously result. This may complete the procedure.
Alternatively, an additional drug therapy may be delivered to further lower
the
thermoregulatory threshold.
An alternate way to lower the thermoregulatory threshold is to use a heating
blanket. As noted above, a common rule-of-thumb is that a patient's comfort
will stay
constant, even if their body temperature is lowered 1 C, so long as a heating
blanket, 5 C
warmer than their skin, is applied to a substantial portion of the surface
area of the patient
(step 114). For a 2 C-body temperature reduction, a 10 C (wanner than the skin
temperature) blanket would be applied. Of course, it is also known that
blankets warmer
than about 42 C can damage patient's skins, this then being an upper limit to
the blanket
temperature. The patient's body temperature may then continue to be lowered by
use of a
heating blanket. For each 1 C reduction in body temperature (step 116), the
heating
23
CA 02524524 2000-07-28
= blanket temperature may be raised 5 C (step 118). After each reduction in
body
temperature, the physician may decide whether or not to continue the cooling
process
(step 120). After cooling, other procedures may be performed if desired (step
122) and
the patient may then be rewarmed (step 124).
It is important to note that the two alternate methods of thermoregulatory
response
reduction may be performed independently. In other words, either
thermoregulatory
drugs or heating blankets may be performed without the use of the other. The
flowchart
given in Figure 11 may be used by omitting either step 104 or steps 114 and
118.
VASOCONSTRICTIVE THERAPIES
Figure 10 showed the more rapid response of the high blood flow organs to
hypothermia than that of the peripheral circulation. This response may be
maintained or
enhanced by applying, as an alternative method of performing hypothermia, a
cooling
blanket rather than a heating blanket. The cooling blanket may serve to
vasoconstrict the
vessels in the peripheral circulation, further directing blood flow towards
the heart and
brain.
An alternate method of performing the same function is to provide separate
vasoconstrictive drugs which affect the posterior hypothalamus in such a way
as to
vasoconstrict the peripheral circulation while allowing heart and brain
circulation to
proceed unimpeded. Such drugs are known and include alpha receptor type drugs.
These
drugs, as well as the cooling blankets described above, may also enhance
counter-current
exchange, again forcing cooling towards the heart and brain. Generally, any
drug or
cooling blanket that provides sufficient cooling to initiate a large scale
cutaneous
peripheral vasoconstrictive response would be capable of forcing the cooling
blood flow
towards the brain and heart (i.e., the "central" volumes). In this
application, the term
"peripheral circulation" or "peripheral vasculature" refers to that portion of
the
vasculature serving the legs, arms, muscles, and skin.
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ADDITIONAL THERAPIES
Turning now from thermoregulatory drugs to additional therapies, the method
and
device according to the embodiments of the invention may also play a
significant role in
treating a variety of maladies involving cell damage.
STROKE
The
present invention may also use blood cooling to substantially reduce platelet
aggregation
as there is a significant reduction in platelet activity at reduced
temperatures. Such
reduction may take place by inhibiting enzyme function, although the actual
methodology
is unclear. This reduction in platelet aggregation, as well as the enhanced
fibrinolysis
noted above, may reduce or eliminate current dependence on such drugs as tPA
or
RheoproTm.
MYOCARDIAL INFARCTION
The above-described venous cooling may also provide a number of benefits for
patients undergoing myocardial infarction.
Current therapies for treating myocardial infarction involve three areas.
Thrombolysis or stenting are used to establish reflow. The oxygen supply is
increased by
directly supplying the patient with oxygen and by vasodilation with nitrates.
And the
oxygen demand is lessened by decreasing the heart rate and the blood pressure.
Devices and methods according to the present invention can work well in -
combination with these current therapies. For example, the device and method
may
lessen the heart's demand for oxygen by providing cooled blood to the heart.
The cooled
blood in turn cools the inner chambers of the heart, essentially from the
inside. Hearts
undergoing myocardial infarction may beat very fast due to an agitated state
of the
victim. However, cooled blood may induce a state of bradycardia that reduces
the
demand for oxygen by the heart per se.
CA 02524524 2000-07-28
To establish reflow and the oxygen supply, the enhanced fibrinolysis,
discussed
above, may also dissolve the clot, allowing more blood flow and more oxygen
delivered
to the heart. As mentioned above, platelet aggregation may be reduced.
Additionally,
conduction through the subendocardium, cooling the heart, may reduce the
overall
metabolic activity of the heart as well as protect the sub endocardium from
cell damage.
It is additionally noted that reflow is often accompanied by reperfusion
injury
which can further damage cells. Neutrophil activation occurs as part of
reperfusion
injury. Hypothermia can limit such activation and thus can limit reperfusion
injury.
Thus, numerous therapies may be delivered by one device. Therefore, e.g.,
currently-employed "beta-blocker" drugs used to reduce heart rate in patients
undergoing
infarcts may not need to be employed in patients undergoing these hypothermic
therapies.
RE-STENOSIS
Another application of the device and method may be in the treatment of
stenotic
arteries. Stenotic arteries are vessels that have narrowed due to a build-up
of tissue
and/or plaque atheroma. Stenotic vessels are treated by angioplasty or
stenting, which
opens the artery. During treatment the vessel wall may be injured. Such
injuries often
(20-50%) cause an inflammatory reaction that eventually causes the vessel to
undergo re-
stenosis after a period of time, which may range from 6-12 months or even
several years
later.
Hypothermia is known to mitigate inflammatory responses. For example, one of
the initial steps in the process of re-stenosis is the migration of
macrophages or white
blood cells to the injured area. Hypothermia can limit this migration.
Hypothermia can
also inhibit reactions and processes initiated by molecules acting in an
autocrine or
paracrine fashion. Hypothermia may also limit the release of several growth
factors (at
the site of injury) such as PDGF and EGF that act in these fashions.
While the invention herein disclosed is capable of obtaining the objects
hereinbefore stated, it is to be understood that this disclosure is merely
illustrative of the
presently preferred embodiments of the invention and that no limitations are
intended
other than as described in the appended claims.
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