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Novel Design of Vascular Clamp to Minimize Vessel Injury Senior Design Final Report 4/26/2011 Vanderbilt University School of Engineering Max Hammond, Nadia Hussein, Neha Patel, Francis Simpson, Eric Walk

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Abstract

The current design of clamps has been fairly unchanged over the past half a century, due

to the lack of acute, macroscopic, visible damage to the vessels. However, studies have

demonstrated significant damage to both the endothelial and smooth muscle layers of vasculature

to which a clamp has been applied, visible on a microscopic level, proportional to the amount of

force applied to the vessel. There are two primary complaints that have prompted the need for a

new vascular clamp design: damage to endothelial layer and length of training time for residents

to use the clamp with their non-dominant hand. The purpose of the Novel Design is to decrease

damage sustained by the endothelium and to reduce training time. Design of the initial prototype

and manufacturing of balloon for occlusion was accomplished using a combination of techniques

including 3D printing, AutoDesk Inventor, and thermal sealing. The results indicate that the

prototype significantly decreased endothelial damage. Percent endothelial relaxation is inversely

proportional to endothelial damage. The percent relaxation for the Debakey clamp was 18.51%

and the percent relaxation for the Hydrogrip clamp was 14.65% compared to the control, which

had a relaxation percentage of 66.55%. The Novel Design had a percent endothelial relaxation of

60.98%. For the comfort category, the Debakey clamp was preferred over the Novel Design with

a p-value of 1.49461E-06. For the ease of use category, the Debakey clamp was preferred over

the Novel Design with a p-value of 3.31852E-05. For the training time category, the Novel

Design was not significantly preferred over the Debakey clamp with a p-value of 0.0814. For the

ingenuity category, the Novel Design was preferred over the Novel Design with a p-value of

2.79256E-05. Our goal that the prototype would reduce the amount of damage to vessels

compared to the current designs was supported by our results. Our goal for the prototype to be

easier to use and more comfortable was not met; however, the goal for decrease in training time

has potential since there was no significant difference between the prototype and the present

clamp and the ingenuity presented by the prototype generates great potential. With some

improvements to the first prototype, Novel Design has the possibility to meet all the goals

presented.

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Introduction

Full occlusion of blood flow through one or more vessels is essential to the success of a

wide variety of surgical procedures, particularly vascular procedures in which the vessels

themselves are the surgical target. This is mainly necessary to prevent hemorrhage, which will

not only potentially lead to patient death, but also interfere with the surgeon‟s view of the

surgical field during a procedure. The primary method used to block these vessels involves the

use of a clamp which resembles a pair of scissors

where, instead of blades, there are grooved or flattened

surfaces which squeeze down on the vessels. The

design of these clamps has been fairly unchanged over

the past half a century, due to the lack of acute,

macroscopic, visible damage to the vessels.1,2

However, studies have demonstrated significant

damage to both the endothelial and smooth muscle

layers of vasculature to which a clamp is applied,

visible on a microscopic level, proportional to the

amount of force applied to the vessel. The application

of force is controlled by the surgeon using a „notch‟ system, in which increasing notches means

greater force and therefore greater damage.3,4

There are two primary complaints that have

prompted the need for a new vascular clamp design.

The first is the previously discussed damage to

vascular endothelium and smooth muscle, which

may cause or contribute to major complications

over time. Vessel injury may result in weakening of

the vessel wall, where an aneurysm may develop;

injury may also trigger some immune response,

result in stenosis, potentially causing thrombus or

embolism, and reduce the vasodilation response to

increased blood pressure. The second complaint is

that training time is too long for surgeons to become

Figure 1: A diagram showing layers of a blood vessel, including endothelium and smooth muscle layers.

Figure 2: Microscopy images of damage caused by current clamps at 3 notches (a,e), 4 notches (b,f), 5 notches (c,g) and 6 notches (d,h).

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comfortable with non-dominant hand control (as the dominant hand is usually otherwise

occupied with other aspects of the procedure). A successful new clamp design would reduce

training time as well as reduce damage to vessels.

When approaching the design of the new clamp, many factors were considered when

evaluating potential success. In addition to the primary goals of reducing training time by 50%

and vessel damage by a minimum of 20%, it was necessary to meet several criteria for the

viability of the design. First, the design must be capable of fully occluding flow through a vessel

for the entire duration of a surgery, and over the full range of blood pressures that are

physiologically possible. The clamp must also be either sterilizable or disposable, to avoid any

opportunity for contamination and infection in the operating room (OR). The size of the clamp is

also an important factor, as space in the surgical field is limited and a device larger than current

designs would likely be received unfavorably. In order to ensure sustainable production of the

device, the final design should be able to be sold for under $2000 per clamp, and must be

profitable to allow for adequate manufacturing.

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Methodology

Design of the initial prototype and manufacturing of balloon for occlusion was

accomplished using a combination of techniques including 3D printing, AutoDesk Inventor, and

thermal sealing. The main body of the

prototype was designed using AutoDesk

Inventor 2011 and was fabricated by

FineLine Prototyping using 3D printing

with WaterShed XC 11122 Normal-

Resolution Stereolithography build in

0.004" layers and post-processed for

biocompatibility per DSM' process for

passing USP Class VI testing. The

balloon for occlusion was fashioned using 1/8” inner diameter tubing and IV bag plastic which

was thermally sealed to create a balloon to be placed around the vessel. A one-way valve

assembly with quick release was fabricated using spare IV tubing parts and connected between

the device and the syringe used for

inflation.

To test the ability of the new clamp

design to hold pressure, an ex vivo test was

performed using a synthetic carotid made

from graft material. The setup for the y-

tubing is shown in Figure 3. The system

was completely filled with water and the

vessel was them placed inside of the clamp.

The balloon was inflated using 10 mL of air

and the vessel was pressurized to 300 mmHg equivalent. The vessel ending was then checked to

make sure that no water was coming out after the clamped region and was used to evaluate the

pressure at which leakage (if any) would occur.

Figure 4: Pressuring testing device to determine how much pressure the clamp will be able to take and still occlude the

vessel.

Figure 3: The prototype. Left most end is the balloon inside the main body of the device. Center is the valve assembly (from left: quick release, one way valve, Y-joint between

syringe and one way valve).

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The testing methodology for evaluating endothelial cell damage as a result of clamp

damage was developed by the Brophy Lab. First a carotid vessel is excised from an animal for

testing and is cleaned to ensure that only the vessel is left and no excess fat or ligaments are still

remaining. The vessel is then cut into

four separate sections for testing. One

segment of the vessel is set aside as a

control. One of each of the remaining

vessel segments is then clamped with a

Debakey clamp, Hydrogrip, and our

Novel Design. After two hours of

clamping, rings are then obtained from the

clamped region and placed into testing

apparatus (see Figure 5). To confirm the

viability of the endothelial cell, the rings

of tissues are placed into a Radnoti Glass Technology Force transducer that is equipped with

PowerLab data acquisition system and chart software. The samples are depolarized using KCl

and their viability is confirmed using a full KCl bath. The endothelial relaxation is then

measured which is inversely proportional to the amount of cell damage. Therefore to compare

each of the clamps multiple samples were run and then 95% confidence intervals were

constructed to assess statistical significance.

Finally, a qualitative survey was constructed to determine the end-user experience and

assess the features of the clamps. Surveys were distributed asking for ratings between 1 and 5

with 1 being poor and 5 being good, in the categories of ease of use, ingenuity, comfort, and

training time. For each category, our Novel Design, the standard Debakey clamp (first use), and

Debakey clamp (now) were evaluated. These results were compiled and statistical analysis

(ANOVA) was conducted to determine if any these categories there was an advantage of our

Novel Design over the standard Debakey clamp. For each ANOVA an alpha value of 0.05 was

assumed.

Figure 5: Mechanical testing apparatus to assess percent Endothelial Relaxation

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Results

Percent Endothelial Relaxation

Endothelial relaxation is an essential

component of the control of

vasodilation/constriction. The current clamps,

Debakey and Hydrogrip clamps cause a disruption of

the endothelial physiology of the vessels which

reduce the percent relaxation in response to physical

and chemical triggers. This endothelial damage has

the potential to create complications resulting from a

localized increase in blood pressure at the site of

former clamping due to limited dilation response of

the vessel. By performing a percent endothelial

relaxation test with the current clamps, our prototype, and an unclamped control vessel, we were

able to compare the endothelial damage caused by each clamping procedure. As that the

endothelium is the most sensitive aspect of the vessel it was chosen for damage assessment. Two

hours of clamping was chosen as a protocol because that represents the upper limit of the

majority of vascular surgeries.

Figure 6 verifies that both the Debakey and Hydrogrip clamps cause significant decreases

in the percent endothelial

relaxation. The percent

relaxation for the Debakey

clamp was 18.51% and the

percent relaxation for the

Hydrogrip clamp was

14.65% compared to the

control, which had a relaxation percentage of 66.55%. Our prototype had a percent endothelial

relaxation of 60.98%. Table 1 shows the 95% confidence intervals for each design. The

confidence intervals of the prototype and the control overlapped indicating there was not a

significant difference between these values in our test. The Debakey and Hydrogrip designs

Figure 6: Percent Endothelial Relaxation for current designs after two hours of clamping.

Table 1: 95% Confidence intervals (CI) for each design.

Control New Clamp Debakey Hydrogrip

Upper limit

of 95% CI 52.73 63.64 21.43 18.18

Lower limit

of 95% CI 80.37 58.33 15.60 11.11

Mean 66.55 60.98 18.51 14.65

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resulted in a percent endothelial relaxation significantly lower than that of both our control and

our prototype.

Qualitative Survey Response Data

Statistical analysis of six surveys was performed and revealed that only in the ingenuity

category did the Novel Design show a significant improvement over the existing designs. One-

way ANOVA was used to compare the designs (see appendix for full results). For the comfort

category, the Debakey clamp was preferred over the Novel Design with a p-value of 1.49461E-

06. For the ease of use category, the Debakey clamp was preferred over the Novel Design with a

p-value of 3.31852E-05. For the training time category, the Debakey clamp was not

significantly preferred over the Novel Design with a p-value of 0.0814. For the ingenuity

category, the Novel Design was preferred over the Debakey clamp with a p-value of 2.79256E-

05.

All surveys were filled out by current residents in vascular surgery who have had

extensive experience with the Debakey clamp. This introduces a bias into the survey results

skewing them towards the Debakey clamp since this is what they were trained on. In order to

properly conduct this survey, residents would need to be presented with each clamp and the

survey on their first day of training. Additionally, that the Novel Design was preferred in only

the ingenuity category implies that the residents see great potential for future improvements to

this design. Although these results indicate that the design did not meet all goals, the survey

results are non-ideal and require reassessment.

Economics

The total cost for the prototype after 100 uses is about $2,260.00. The total cost for the

fully disposable clamp after 100 uses is about $2,202.00. The break down for each component‟s

cost analysis is shown in Table 2. Overall, the goal for cost was met because the prototype fell in

the $2000.00 range and was comparable to the current design. In fact, the prototype was slightly

less than the current clamp.

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Conclusion:

Our hypothesis that the prototype would reduce the amount of damage to vessels

compared to the current designs was supported by our results. Based on the percent endothelial

relaxation testing, the Novel Design significantly reduced the damage to the vessel. The percent

endothelial relaxation of the prototype was not significantly different from the control based on

the overlap of the confidence intervals for both.

Based on the qualitative survey results from current surgery residents the Debakey clamp

was favored over the prototype for ease of use and comfort. The prototype was favored over the

Debakey for ingenuity. There was no significant difference between the training times for the

two clamps. Although the goals for ease of use and decrease in training time was not met with

the prototype, the future changes for the clamp, combined with a survey preformed on first year

residents, would potentially change the results.

Future Directions

There were three major flaws with the design: material of the main body, shape of the

main body and the closure mechanism. Fortunately, these flaws do not invalidate the premise of

the design (the use of a balloon in a plastic housing to achieve occlusion). The main body of the

clamp was made of a brittle plastic that is biocompatible and withstands ethylene oxide

sterilization well. In a disposable production model, sterilization method is less important as long

Table 2: Cost analysis of current design compared to prototype and estimates of full scale production cost for novel design.

Item Current Design Prototype Estimated Full Scale Cost (fully

disposable)

Plastic Parts --- $262.00 $15.00

Rubber Parts --- $40.00 $3.00

Metal Parts $1.00 $0.20

Sterilization By Manufacturer --- --- $2.00

MSRP (10% profit) ~$1760.00 $333.30 $22.02

Sterilization By User (per use) $5.00 $2.00 ---

Total Cost for 100 uses ~$2,260.00 --- $2202.00

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as it is compatible with one of them. Ideally a less brittle plastic would be used so as to avoid

breakage in manufacturing. The shape of the handle could also be improved to be slightly thicker

so as to avoid breaks during manufacture. Additionally, the diameter of the opening for the

vessel was designed to the maximal size of the carotid in a human; however the thickness of the

balloon was underestimated. Thus a larger diameter is required. Finally the closure mechanism

needs to be adjusted in two ways. First, the hinge mechanism needs to be changed such that the

parts do not separate when the balloon is inflated. Second, the lever arm needs to be compounded

so as to provide greater mechanical advantage (i.e. a small movement at the distal end creates a

big movement at the proximal end). The first problem is solved simply, creating a series of

interlocking fingers along the joint and running the hinge pin through them to create a “piano”

style hinge. The second problem is more complex requiring the careful design of a series of pivot

points along the arm to act as a mechanical amplifier (much as the bones in the inner ear). These

adjustments should help to alleviate the concerns expressed in the surveys by the residents;

consideration should be given to methods for automatic inflation upon closure to further address

these concerns. With these adjustments to the design it should be more adept in in-vivo

scenarios; the current prototype was sufficient, however, for proving that it is possible and

practical to occlude a vessel with an inflatable cuff.

References:

1. Darçin OT, Cengiz M, Özardali I, et al. Pressure-controlled vascular clamp: a novel device for

atraumatic vessel occlusion. Ann Vasc Surg 2004;18:254-256.

2. Gersak B, Trobec R, Krisch I, et al. Loss of endotheliummediated vascular relaxation as a

response to various clamping pressures. Eur J Cardiothorac Surg 1996;10: 684-689.

3. Margovsky AI, Lord RS, Meek AC, et al. Artery wall damage and platelet uptake from so-

called atraumatic arterial clamps: an experimental study. Cardiovasc Surg 1997;5:42-47.

4. Margovsky AI, Chambers AJ, Lord RS. The effect of increasing clamping forces on

endothelial and arterial wall damage: an experimental study in the sheep. Cardiovasc

Surg 1999;7: 457-463.

5. Zhang Y, Luo Y, Kodaira S, et al. Application of Shape Memory Alloy Pressure-Controlled

Vascular Clamp for Atraumatic Vessel Occlusion. Ann Vasc Surg 2009; 23: 813-820

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Appendix A: ANOVA Results and Survey Results

Comfort

Comfort Novel Design Original (first use) Original (current)

User 1 4 4 5

User 2 2 4 5

User 3 2 4 5

User 4 3 4 5

User 5 3 4 5

User 6 3 4 5

Average 2.833333333 4 5

Stdev 0.752772653 0 0

Anova: Single Factor

SUMMARY

Groups Count Sum Average Variance

Column 1 6 17 2.833333333 0.566666667

Column 2 6 24 4 0

Column 3 6 30 5 0

ANOVA

Source of Variation

SS df MS F P-value F crit

Between Groups 14.11111111 2 7.055555556 37.35294118 1.49461E-06 3.682320344

Within Groups 2.833333333 15 0.188888889

Total 16.94444444 17

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Ease of Use

Ease of Use Novel Design Original (first use) Original (current)

User 1 3 4 5

User 2 3 4 5

User 3 2 5 5

User 4 3 4 4

User 5 3 3 5

User 6 2 5 5

Average 2.666666667 4.166666667 4.833333333

Stdev 0.516397779 0.752772653 0.40824829

Anova: Single Factor

SUMMARY

Groups Count Sum Average Variance

Column 1 6 16 2.666666667 0.266666667

Column 2 6 25 4.166666667 0.566666667

Column 3 6 29 4.833333333 0.166666667

ANOVA

Source of Variation

SS df MS F P-value F crit

Between Groups 14.77777778 2 7.388888889 22.16666667 3.31852E-05 3.682320344

Within Groups 5 15 0.333333333

Total 19.77777778 17

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Training Time

Training Time Novel Design Original (first use) Original (current)

User 1 2 1 1

User 2 2 3 2

User 3 3 1 1

User 4 2 3 2

User 5 3 2 2

User 6 3 1 1

Average 2.5 1.833333333 1.5

Stdev 0.547722558 0.98319208 0.547722558

Anova: Single Factor

SUMMARY

Groups Count Sum Average Variance

Column 1 6 15 2.5 0.3

Column 2 6 11 1.833333333 0.966666667

Column 3 6 9 1.5 0.3

ANOVA

Source of Variation

SS df MS F P-value F crit

Between Groups 3.111111111 2 1.555555556 2.978723404 0.081404169 3.682320344

Within Groups 7.833333333 15 0.522222222

Total 10.94444444 17

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Ingenuity

Ingenuity Novel Design Original (first use) Original (current)

User 1 5 3 3

User 2 5 1 1

User 3 5 2 2

User 4 4 1 1

User 5 4 2 2

User 6 5 3 3

Average 4.666666667 2 2

Stdev 0.516397779 0.894427191 0.894427191

Anova: Single Factor

SUMMARY

Groups Count Sum Average Variance

Column 1 6 28 4.666666667 0.266666667

Column 2 6 12 2 0.8

Column 3 6 12 2 0.8

ANOVA

Source of Variation

SS df MS F P-value F crit

Between Groups 28.44444444 2 14.22222222 22.85714286 2.79256E-05 3.682320344

Within Groups 9.333333333 15 0.622222222

Total 37.77777778 17