IV Cooling System for Hypothermia
Advisor: Dr. James Menegazzi
April 17, 2007
Table of Contents
Specific Aims ............................................................................................................................. 3
Significance ................................................................................................................................ 6
Preliminary Work ..................................................................................................................... 9
Methods .................................................................................................................................... 11
Conclusion …………………………………………………………………………………... 21
References ................................................................................................................................ 22
In previous studies, researches have found that cardiac arrest often leads to severe
neurological damage.2 During cardiac arrest, a cession in blood flow for greater than five
minutes results in a chemical cascade in the body results in serious cerebral impairment.
However, if the body temperature could reach mild (34°C) to moderate (30°C)
therapeutic hypothermia immediately after cardiac arrest, the neurological outcome
would be much more improved as well as the mortality rate would be decreased.
Decreasing the body temperature lowers the amount of oxygen that is demanded by the
The proposed goal of this Phase I project is to create a cooling device to begin the
process of inducing mild hypothermia easily and quickly after cardiac arrest. This device
could be used by EMS and other first aid personals to help the patients before they get to
the hospital. In order to reach the best and fastest cooling results, this device functions by
cooling the body both internally and externally. Cooled saline flowing through standard
IV tubing, which is exposed to an ammonium nitrate – water solution (approximately 0°
C), will be infused into the body in an effort to induce mild hypothermia. Additional
external cooling will occur by placing the device on the patient’s chest.
Our Phase I specific aims are:
1. Design an IV cooling system for cardiac arrest patients to achieve the
Selection of the concentration of ammonium nitrate in the coolant
Three ratios (1:1, 2:1, 1:2) of ammonium nitrate to water
will be tested to determine which concentration will achieve
the minimum temperature for the longest period of time.
The less ammonium nitrate needed for the device the better
because it will lead to a cheaper manufacturing price.
Amount of tubing needed and the design of the device.
Multiple prototypes will be designed of similar nature to
decide which will cool the saline to the lowest temperature
while maintaining a good flow rate. It is desired to flow 2 L
of saline into the patient within 15 minutes (2.22 cc/ sec).
This is the typical amount infused in a cardiac arrest patient
on their way to the hospital. The final prototype will be
chosen based on flow rate and the temperature of the saline
as it would enter the patient.
The size of the casing and material selection.
Size of the casing will be based on the size of an average
male’ chest. Material will be chosen on its thermal
conductivity, durability and ease of heat sealing.
The device will not induce mild hypothermia on its own.
However, it will begin the process on the patient’s trip to the
hospital at which time more advanced systems can be used to keep
the patient in the mild hypothermia state for 12-24 hrs.
2. Fabricate prototypes for testing.
A SolidWorks model will be created.
A prototype will be fabricated manually in the machine shop with
help from Andy Holmes. Various tools will be used to cut the
manifold and drill the holes.
3. Test prototypes in vitro.
Saline will flow from a one liter saline bag with a pressure bag
attached to it, through standard IV tubing to our activated
(ammonium nitrate and water already mixed) device which will
begin the cooling of the saline. The cooled saline will then flow
out of the device and into a patient (a beaker), where the average
temperature will be recorded. The goal is to have the saline reach
a temperature of 10° C less than normal room temperature with a
flow rate as close as possible to 2.22 cc/ sec.
In their 2006 update, the American Heart Association estimates, 163,221 out-of-
hospital cardiac arrests will occur annually in the US.1 On average EMS treatment of
out-of hospital cardiac arrest occurs in 107,000 – 240,000 cases annually1. It has been
documented that after cardiac arrest with no blood flow for a period of time greater than
five minutes, cerebral brain damage due to ischemia will result.2
Therapeutic hypothermia has been in research literature as early as the 1950’s but
was widely ignored until the new millennium. In 2002, two publications shed light on the
possibility of the treatment of out-of-hospital cardiac arrest with mild therapeutic
hypothermia (30°C – 34°C).2,3 These publications both involved independent
randomized controlled studies and demonstrated significant improvement for comatose
survivors of out-of-hospital cardiac arrest with ventricular fibrillation. Based on the
evidence supported by the aforementioned publications, the Advanced Life Support Task
Force of the International Liaison Committee on Resuscitation (ILCOR) recommended in
2003, unconscious adult patients of cardiac arrest caused by ventricular fibrillation with
spontaneous circulation should be cooled between (32°C – 34°C) for 12 to 24 hours and
cooling may benefit other types of in-hospital cardiac arrest.4
The benefit of therapeutic hypothermia for out-of-hospital comatose cardiac arrest
patients focuses on the ability to limit cerebral ischemia. The chemical effect of cerebral
ischemia has been shown to cause an energy depletion, ion pump failure, and release of
free radicals. These free radicals and also the creation of excitotoxic agent created also
invoke an increase in body temperature.7 Mild hypothermia treatment for cardiac arrest
has shown a decrease in length of hospital stay, reduction of hospital mortality, and
survival rates after one year.8
The cooling of intravenous fluids has evolved into an increasingly viable and
beneficial method because it can be preformed before the patient arrives at the hospital.
Examples of these types of products such as the ice cold Ringer solution demonstrate
this.9 The device forming the basis of this Phase I proposal relies on the principle of
attempting to quickly cool intravenous fluid in an effort to lower the blood temperature
and thereby decreasing the oxygen demand of the brain. This device enables the patient
to be treated with therapeutic hypothermia while being transported to a hospital. The
quicker a cardiac arrest victim can be treated with therapeutic hypothermia the greater the
potential neurological benefit that can be received. Since brain damage occurs with no
blood flow for more than five minutes, the issue of time is of utmost importance and
implementation of mild therapeutic hyperthermia as close in time to the cardiac arrest is
Surveys have been conducted of the health care industry exploring the lack of
compliance with the recommendations of the ILCOR.5,6 Abella et al. noted to the
question of “Have you ever utilized hypothermia in a patient after resuscitation?”, Over
71% of critical care providers and 95% of emergency medicine provides stated no.6 The
conclusions that the Abella group reached for the above mentioned statistics were the
following: lack of awareness of supporting data, technical constraints, and lack of
hypothermia protocol led to an under-use of mild hypothermia. We have developed a
protocol for implementation of our device and a method of usage, which does not
infringe on their natural ability of the emergency medical professional, provides to
perform their life support tasks.
Under a specified set of parameters, we tested the saline temperature cooled by the
chemical bag model. The total tubing length is 4ft, which makes 6 turns inside the device.
The initial temperature inside the device is 8°C, and the temperature of saline external to
the device is 20.6°C. The model setup is shown below:
Figure 1. The chemical cooling package and IV tubing. Outside view (left). Inside View (right).
We ran four trials to test the temperature drop of saline. Two of them were under
pressurized condition and two of them were not. The test results are shown in Table 1:
Table 1: Four trials and the results in preliminary study.
Trial 1 (unpressurized, gravity driven):
Time (min) Temperature (°C)
Trial 1 (pressurized)
Time (min Temperature (°C)
Trial 2 (unpressurized, gravity driven):
Time (min) Temperature (°C)
Trial 2 (pressurized)
Time (min) Temperature (°C)
From the results above, the saline was not cooled enough to reach the temperature we
want (10° C less than standard room temperature). The number of tubing turns inside the
device may need to be increased and the IV fluid temperature needs to be much colder to
Specific Aim 1: Design
Ammonium Nitrate Concentration Selection.
In order to maximally decrease the patient’s body temperature simply by the
saline entering the body through a peripheral IV, it is necessary that the temperature of
the saline is as close to freezing (0°C) as possible. We will do this by taking advantage
of the endothermic chemical reaction that occurs between the coolant composed of
ammonium nitrate and water. When the two chemicals are mixed together, they
immediately react to rapidly decrease the temperature of the solution. To determine how
close to freezing this chemical reaction can get, we will experiment using numerous
ratios of coolant to water, keeping volume constant: 1:1, 1:2, and 2:1. The different
ratios are shown in Table 2. It should be noted that commercially sold ice packs, as well
as information listed in patents, that the ratio of ammonium nitrate to water is not a molar
ratio, but instead a gram ratio. Therefore, the ratios (1:1, 1:2, 2:1) listed here are gram
ratios. We will test each of these ratios, recording the average temperature in the beaker
(“patient”), plotting this average temperature over a 15 minute period and determining
which ratio achieves the most amount of cooling for the longest period of time.
Table 2: Concentrations that will be tested to determine ratio of ammonium nitrate
Test Water (mL) Ammonium
1 500 500
2 666 333
3 333 666
In general, we expect the temperature to decrease as the amount of coolant
increases. Using a digital temperature probe, the temperature will be continuously
monitored for 15 minutes from the time the chemicals are mixed. The chemicals will be
mixed manually at first then left alone to simulate what will actually occur when using
the device in vivo. We will only measure the temperature for the first 15 minutes because
the maximum amount of cooling occurs between 10 and 15 minutes and the device is
only specified to be used for 15 minutes. After 15-20 minutes, the temperature will
slowly increase until it reaches room temperature. The final concentration of coolant to
water will be chosen based on the experimentally lowest recorded temperature for the
longest amount of time.
Tubing Length and Number of Turns
The IV fluid must be exposed to the coolant for a period of time long enough to
adequately decrease the patient’s core body temperature. This amount of time has been
approximated to be 15 minutes Standard IV tubing (4 mm internal diameter) will be used
in the device. There will be two different prototypes of the device, the tubing set up in
series and also set up in parallel like a classic heat exchanger.
Chemical Ice-Bag with Internal
Figure 1: Diagram showing the tubing set up in series. In this prototype the tubing
will be snaked in series
Figure 2: Manifolds used to set the tubing up in parallel.
There is a balance between tubing length and amount of time required for the
saline to reach the patient, which depends on the flow rate. The longer the tubing inside
the device, the slower the flow rate, the longer it will take the saline to enter the body.
The goal is to have the fluid enter the body at a maximum flow rate, while still having a
cooling effect. We will control these factors by altering the total tubing length for the
prototype where the tubing is set up in series and altering the length of tubing on each
bridge of the manifold. The length of tubing will be determined theoretically estimating
the surface area needed to achieve the required cooling, then determining the length of
each tube. It has been estimated from theoretical calculations, using an equation derived
from the conservation of mass through a tube, that the length of each tube in the manifold
should be about 10 inches long or the length of tubing for the prototype in series should
be about 4 feet long. These two prototypes will be testing along with some slight
variations. We will also test minivolume tubing (same length as the standard IV tubing)
for the prototype with tubing in series to test if the increase in surface area decreases
saline temperature. We will also test connecting 2 manifolds together to increase the
residence time of the saline in the device as shown in Figure () and ().
Figure 3: Prototype with tubing in parallel. In this device, there are two rows of
Figure 4: Prototype with tubing in parallel. In this device, there is one row with 32
tubes across and each manifold is connected by a T-connector.
The flow rate will be controlled by adjusting the amount of force that the
pressure bag is exerting on the saline. There is an indicator on the pressure bag, a white
zone, a green zone, and a red zone. The white zone indicates minimal pressure on the
bag, the green zone indicates maximal pressure without the bursting of the bag, and the
red zone is a danger zone where the pressure will automatically deflate. The flow rate
will be kept at a maximum by keeping the pressure in the green zone (about 300 mmHg).
Case Size and Material Selection
We will create a rectangular case that will lie across the patient’s chest which
should maximize the cooling effects. The case will be created to fit the tubing inside the
device, but the case has been estimated to be about one foot by one foot (based solely on
an estimation of adult patient’s chest sizes). The case will be flexible, because it needs to
be able to be cracked and shaken to break the water sac inside that will induce a chemical
reaction. Although a non conductive material would be best to maintain a cool
temperature inside the device, we also want there to be external cooling to the patient so
the simplest material will be selected. In this case, the simplest material is the same
material currently used in the commercially available ice packs. Polyethylene will be the
material used in the device. It is flexible, thermally conductive, water-resistant, durable,
and can be easily sealed so heat will easily transfer from the device to the tubing as well
as the patient’s chest.
Specific Aim 2: Fabrication
We will fabricate the device by hand. Using the machine shop, with the help of
Andy Holmes, we will hand fabricate and assemble the device. A band saw will be used
to cut the hard portion of the manifold (dacron tubing). Holes will be cut into the dacron
tubing with a mill and a lathe, and various hand tools will be used to tap the holes in
order to get connectors to connect to the holes.
Specific Aim 3: Testing
All testing will be done in vitro. In each of these tests, the experiment will be set
up as shown in Figure (), including a pressure bag with one liter of saline, an extension
set to connect the saline bag to the device (ID of 4 mm), the device, and another
extension set (ID of 4 mm) to connect the device to the arm of the patient (“the beaker”)
where the core body temperature (“temperature of saline inside the beaker”) will be
measured. This same set-up exists for each of the prototypes. The average temperature of
the saline inside the beaker will be measured using a digital thermometer each minute for
Ammonium Nitrate Concentration Selection
The first test was performed to select the proper ammonium nitrate concentration
that would optimize our ratio to provide the maximum amount of cooling for the longest
period of time. Table 3 (A, B and C) shows the temperature of the coolant solution over
15 minutes for three separate ammonium nitrate and water ratios. It was found that both
the 1 NH4NO3: 1 H2O ratio and the 2 NH4NO3: 1 H2O ratio resulted in similar outcomes.
In both the temperature dropped to a minimum of -4° C and remained under 0° C for 15
minutes. These were much better than the 1 NH4NO3: 2 H2O ratio in which the
temperature never went under 2° C. In the end, a 1 NH4NO3: 1 H2O was decided to be
best because it would result in a cheaper manufacturing cost as not as much ammonium
nitrate would be needed.
Standard IV Tubing vs. Minivolume IV Tubing
It was thought that by increasing the surface area exposed to the coolant by using
minivolume IV tubing it would result in a lower saline temperature. Table 4 shows the
temperature of the saline after flowing through 71” of tubing (A – standard, B-
minivolume). The outer diameters, inner diameters and wall thicknesses are also
reported. It was discovered that after 15 minutes the temperature of the saline flowing
through the minivolume tubing was only 0.2° C cooler than that flowing through the
standard IV tubing. It was decided this was not worth the 0.4 cc/min decrease in the flow
rate. Flow rate was already the greatest concern and any further decrease from a 0.5
cc/min flow rate would be unacceptable.
Table 3: Temperatures of ammonium nitrate and water solutions over 15 minute
A B C
1 NH4NO3: 1 H2O 2 NH4NO3: 1 H2O 1 NH4NO3: 2 H2O
Elapsed Elapsed Elapsed
Time Temperature Time Temperature Time Temperature
(min) (Celsius) (min) (Celsius) (min) (Celsius)
0 10 0 8 0 10
1 0 1 -2 1 4
2 -3 2 -4 2 4
3 -4 3 -3 3 4
4 -4 4 -3 4 2
5 -4 5 -3 5 2
6 -3 6 -2 6 2
7 -3 7 -2 7 2
8 -2.5 8 -2 8 2
9 -2 9 -1.5 9 2
10 -1.5 10 -1 10 2
11 -1 11 -1 11 2
12 -0.5 12 -1 12 2
13 -0.5 13 -0.5 13 3
14 -0.5 14 0 14 2
15 0 15 0 15 4
16 0.5 16 0 16 4
17 1 17 0.5 17 5
18 1 18 1 18 5
19 1.5 19 1 19 4
20 2 20 1.5 20 5
Average -1.2 Average -1.1 Average 3.1
Table 4: Temperature recorded as a function of time for the prototype where the
tubing is in series. Note that the length is 2 feet longer than proposed in the methods
section due to ordering restraints. It was assumed to be more beneficial to have
tubing that was longer than shorter for heat transport purposes.
Standard IV Tubing Minivolume IV Tubing
OD= 0.140" OD=0.0895"
Time (min) Temp (deg C) Time (min) Temp (deg C)
1 16.2 1 17.9
2 14.9 2 17.8
3 14.1 3 15.5
4 14.8 4 13.9
5 14.3 5 12.9
6 14.5 6 12.7
7 14.4 7 12.9
8 14.5 8 13.3
9 14.8 9 13.9
10 14.9 10 14.6
11 15 11 14.9
12 15.4 12 15.1
13 15.1 13 14.9
14 15.1 14 14.9
15 15.3 15 15.1
AVERAGE 14.9 AVERAGE 14.7
FLOW RATE (cc/min) 0.5 FLOW RATE (cc/min) 0.1
Starting Temp of
The results of our final prototype may be found in Table 5. This was a single
manifold design with sixteen 10” standard IV tubes. The Solid Works design may be
seen back in Figure 2. Two alternative designs were also tested (Figure 3 - 2 rows of 16
tubes and Figure 1- 1 row of 32 tubes) but the pressure drop was too large to obtain a
flow rate any where near acceptable for these designs to work. Our prototype cooled the
saline to a minimum of 10.4° C while remaining under 10.3° C for 15 minutes. The flow
rate was 1.11 cc/sec which was half of the 2.22 cc/sec that we had wished to achieve.
Table 5: Temperature recorded as a function of time for the final device (1 row of 16
Time (min) Temp (F) Temp ( C )
1 72 22.2
2 51.2 10.7
3 51.1 10.6
4 50.8 10.4
5 50.1 10.1
6 50 10.0
7 50.8 10.4
8 51.4 10.8
9 50.4 10.2
10 50.8 10.4
11 50.3 10.2
12 50.8 10.4
13 50.6 10.3
14 50.9 10.5
15 50.5 10.3
Q 1.11 cc/sec
After thorough testing, we developed a device that will begin the process of
inducing mild hypothermia in patients suffering from cardiac arrest. The device is best
used when administered within 5 minutes of the stoppage of blood flow in the patient and
when not used for a period of time over 15 minutes. Saline will flow from a pressurized
saline bag through standard IV tubing into our device. Our device will cool the saline to
~10° C as the tubing it flows through is exposed to a 1:1 ratio of ammonium nitrate and
water. The saline will exit the device through standard IV tubing flowing at 1.11 cc/ min
with an temperature of 10.4° C over 15 minutes. In summary, 1 L of cooled saline will
be infused in 15 minutes. This is a decrease of 50% from the normal 2 L of saline that is
infused to cardiac arrest victims, but we believe that this process will better the
neurological outcome of the patient as well as reduce the chance of mortality. It should be
noted that further in vivo tests still need to be performed to gain a better understanding of
the situation. These tests are planned and will be done before the device is put on the
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