2. Summary
• Vaso-occlusion, which is the obstruction of
blood flow in a vessel, leads to ischemia,
chronic pain, and, if left untreated, tissue
death (Yale et. al. 1349-1356)
• Caregivers are routinely unable to correlate the
magnitude of a vaso-occlusive event and pain
in patients with sickle cell disease.
3. Summary
The subjective pain scale is the primary method of
detection
• Patient ranks his/her pain on a scale of 1-10
• Contains no biometric data that relates severity of
vaso-occlusion to pain
4. Summary
• Purpose: develop a modified pulse oximeter that
will measure oxygen saturation or perfusion
levels in tissue.
• Goal: determine a correlation between the
oxygen levels and/or perfusion within the region
of pain and the level of pain the patient is
experiencing
• The device will, hopefully, lead to more efficient
treatment
5. Sickle Cell Disease
• Malformation of hemoglobin
• Results in sickle-shaped red blood cells with
altered function and lifespan
• Complications include painful vaso-occlusive
episodes, ACS, stroke, pulmonary
hypertension, multi-organ damage, decreased
life-span (Conran 1-2)
• Affects 70,000-100,000 individuals in the US
(SCDAA.com)
6. Vaso-Occlusion
• Most common complication of sickle cell
disease
• Painful
• Can occur in arms, legs, chest, abdomen
(American Family Physician 1027)
8. Pain
• Caused by infection and/or ischemia
• Pain occurs in legs, arms, lower back, knees,
chest, abdomen
• 5% of patients with sickle cell disease have 3-10
pain episodes per year
• Pain crises are the primary reason for ER visits
10. Pain Management
Common Opioids Used to Treat Mild to Moderate Pain in Sickle Cell Disease
Drug Usual oral starting dosage in adults Comments and precautions
Codeine 30 to 60 mg Every 3 or 4 hours Available in liquid or tablet form,
alone or in combination with
acetaminophen
Side effects: impaired ventilation
(histamine release possibly
triggering bronchospasm) and
increased intracranial pressure
as a result of carbon dioxide
retention
Oxycodone (Roxicodone) 10 to 30 mg every 4 hours Often used in combination with
acetaminophen, which limits
safe dosage to 12 tablets per day
(about 4 g of acetaminophen)
Side effects: similar to those of
codeine
IM = intramuscular; IV = intravenous; SC = subcutaneous.
*—Single-dose studies determined that the relative potency is 6:1; with repetitive doses, this ratio changes to 3:1.
11. Pain Management
Equianalgesic dosages Usual starting dosage in adults
Drug Oral/IM potency IM Oral Oral Parenteral
Morphine 6* 10 mg 60 mg 15 to 30 mg every 0.1 to 0.15 mg per
(Duramorph) 4 hours kg every 3 or 4
hours
Hydromorphone 5 1.5 mg 7.5 mg 2 to 4 mg every 4 1 to 2 mg every 4
(Dilaudid-Hp) to 6 hours to 6 hours
Meperidine 4 75 mg 300 mg 50 to 150 mg 75 to 100 mg
(Demerol) every 3 or 4 hours every 3 or 4 hours
Levorphanol 2 2 mg 4 mg 2 to 4 mg every 6 Up to 1 mg IV
(Levo-Dromoran) to 8 hours every 3 to 6 hours;
1 to 2 mg IM or SC
every 6 to 8 hours
IM = intramuscular; IV = intravenous; SC = subcutaneous.
*—Single-dose studies determined that the relative potency is 6:1; with repetitive doses, this ratio changes to 3:1.
13. Pain Validation
• Pain scale—subjective
• CT*
• Chest X-Ray*
*Not ordered regularly—very expensive
Need: A reliable, non-invasive, and inexpensive device
to provide correlating data between the occurance and
severity of vaso-occlusion and the pain that the patient
is experiencing
14. Specifications
• Vaso-occlusion reduces the flow of oxygenated
blood, which leads to a reduction of oxygen within
the tissue.
• Reduced oxygenation leads to tissue damage and
pain.
• The device proposed will adapt the principles of
photoplethysmography to measure the oxygen
saturation level at the site of pain.
15. Specifications
Product Specification Design Specification
Pulse oximetry will be used to detect the varying levels of
1. Detecting varying levels of blood oxygen
blood oxygen saturation. This must be able to read blood
saturation
oxygen saturation between 70% and 100% (ISO).
The device will be able to detect a fraction of the light that
2. The device must be able to obtain is originally emitted into the arm. The fraction will be
measurements through 5 inches of flesh determined using Beer’s Law and the optical properties of
human tissue.
No exposed wires will be present in the device, and the
3. Electrical components must be isolated
leakage current will meet IEC standards (under 300µA).
This includes the time taken to attach the device to the
patient, the time required for the device to take
4. Data acquisition must take less than 5 minutes
measurements, and the time for the device to interpret
the measurements taken
This device must be reliable with no false negatives. This
5. Reliability
will follow ISO Standard 80601-2-61-2011.
The device should not cause any discomfort during use. It
6. Comfort/Ease of Use should be easy to place on the patient and should be
easily removed
16. Alternative Methods
Method Specifications Met Pros Cons
Non-invasive May be time consuming to find the exact
location of the vaso-occlusion
Pulse Oximetry All inexpensive
If the occlusion is too great, a signal may not be
easily adaptable for our use determined
Non-invasive
All May be time consuming to find the exact
Perfusion Index location of the vaso-occlusion
inexpensive
Expensive (Camera > $5002)
Non-invasive
Fast Frame
1,3
“SpO2 Camera”1 Only measures O2 at surface
Non-invasive Expensive (Camera>$10003)
Gives a general view of temperature in the Only measures temperature at surface
Thermal Imaging 1,3
body
Can only work if vaso-occlusion causes a
Fast data acquisition temperature difference in skin
Sources: 1(Kamshillin 996-1006); 2EdmundOptics.com; 3Neo-Bits.com
18. Further Research
Further research is needed in the following areas:
• Pathology of vaso-occlusion
• Location of vaso-occlusion
• Frequency of vaso-occlusion
• Size of affected area
• Time in which ischemia occurs
• Treatments for vaso-occlusion
(not pain treatment)
19. Specific Aims
1. Confirm that a Vaso-Occlusive Crisis Can be
Detected
– Blood Oxygen Saturation
– Pulse Oximetry
– Photoplethysmography
20. Specific Aims
2. Develop a Device that Can Measure the
Varying Oxygenation Levels
– The device will be developed using various
programming software and hardware
–LabView
–LEDs
–Photodetector
21. Specific Aims
3. Design the Device so that it can be Attached
to a Patient’s Arm of Varying Sizes
– This device should be able to adjust to
varying thicknesses.
–Adjustable armband
22. Specific Aims
4. Find a Correlation Between Oxygen
Saturation in the Blood and Pain
– A pain scale can be created that ranges
from one to ten.
– Each number on the pain scale can correlate
to a specific range of oxygen saturation
levels.
24. Preliminary Data
• Methods of Data Collection
– Vaso-occlusive crisis was simulated
• A tourniquet was used to do this
– Different pulse oximeters were used
• Nano Tracker
• Medtronic Lifepak 12 Clinical Pulse Oximeter
• AD Instruments MLT321 Pulse Oximeters
25. Preliminary Data
Table 1 - DATA FROM PHOTOPLETHYSMOGRAPH (NANO TRACKER)
Normal O2 Normal O2 O2--V-O Mimic O2--V-O Mimic
Left Arm Right Arm Left Right
Subject 1 n/a 0.93 n/a 0.74
Subject 2 0.95 0.97 0.76 0.8
Subject 3 0.97 0.97 0.78 0.82
STDV L 0.11030 STDV R 0.09786
n=2
p=0.0035 - Right Arm
n=3
p=0.0055 - Left Arm
26. Preliminary Data
Table 2 - DATA FROM MEDTRONIC LIFEPAK 12 PULSE OX
Normal O2 Left O2--V-O Mimic
Perfusion Index
Arm Left
Subject 1 0.97 0.86 Decreased
Subject 2 0.96 0.88 No Change
Subject 3 0.98 0.88 Decreased
STDV 0.053821
p=0.0004
n=3
27. Preliminary Data
Table 3 - DATA FROM AD INSTRUMENTS PULSE OX
O2 Experimental
Normal O2
Arm
O2--Experimental
(Normal
Control Arm
Conditions)
Subject 1 0.97 0.97 0.92
Subject 2 0.95 0.96 0.91
Subject 3 0.974 0.983 0.953
Subject 4 0.99 0.99 0.96
p=0.0540—Control vs. Experimental
STDV Exp 0.028116
p=0.0285—Experimental (Normal Conditions) vs.
n=4
Experimental Conditions
28. Preliminary Data
• T-test Values
– Table 1
• p=0.0035 - Right Arm
• p=0.0055 - Left Arm
– Table 2
• p = 0.0004
– Table 3
• p = 0.054 – Control vs. Experimental
• p = 0.0285 – Experimental (Normal Conditions) vs.
Experimental Conditions
29. Purpose
• Detect Low oxygen concentration in
extremities.
• Easy and cheap diagnostic technique for vaso-
occlusion patient.
• Early diagnosis ease the treatment and
prevent further damage.
30. Working Principle
• Pulse Oxymetry consist of Red(R) and
infra red (IR) light emitting LEDs and a
photo detector/s.
• Oxygenated and de-oxygenated
hemoglobin have differential light
absorption rate.
– Oxygenated hemoglobin absorbs more
infrared light and deoxygenated
hemoglobin absorbs more red light.
• Photo detector measures the
transmitted lights and calculate R/IR
ratio.
• R/IR ratio determines the oxygen blood
concentration.
31. Modification
• The pulse Oxymetry will be modified to fit in
the extremities.
• High power LEDs will be used for larger parts.
• Two oximeters will be used for control and
experimental data.
• Multi-array detector will be used if needed
32. Proposed Solution
• Single source multiple detector can be
used.
• Uneven distribution on the detector can
be analyzed mathematically.
• The output in the detector can be
averaged out to find the occlusion.
• Non-linear transmission of the light can
result the uniform result.
• Experiment can be conducted to test the
linear behavior of the device.
33. Proposed Solution
• Rotating LEDs with aligned
detectors can be designed.
• Signal from detector can be
reconstructed using convolution.
• Complicated design but it can
be promising solution.
• CT scan uses same mechanism
to create the cross sectional area.
34. Cost Structure
Per Unit Price in Number of Number of Total Our Cost
Components
Price ($) bulk($) pieces in Bulk units used Price ($) ($)
Op Amp 0.92 12 11.04 11.04
Resistors 0.05 2.33 50 20-40 13.98 13.98
Capacitor 0.12 2.9 25 4-8 29.00 29.00
LED 660/940 4.64 5 25.00 25.00
Bread Board 18.00 1 18.00 18.00
ArmBand 60.00 1 60.00 60.00
Photodetector 44.00 5 220.00 220.00
Analog to Digital
280.00 1 280.00 Donated
Converter
Computer with
3200.00 Donated
Software
Travel 150.00 150.00
Total Price 4007.00 527.02
35. Testing
• The device has to be calibrated for each
individual.
• The device uses its data and compares with
the control data.
• Device will correlate the severity of the vaso-
occlusion measuring the blood oxygen
concentration.
36. Design Specification
• Our device
will utilize an
adjustable arm-
band design.
• We will use
multiple LEDs
and detectors
37. Benefits of a Multiple LED system
• Produces more light which allows
detector to see dark spots better
• Even if the crisis occurs outside of the
emitance of the LED, our detectors can
identify a crisis
38. Technique
• We will use two pulse oximeters
• This can allow us to get a
baseline reading while
simultaneously attempting to
identify a crisis
• Preliminary testing has proven
this method to be viable
39. Recreating a vaso-occlusion
• Vaso-occlusion causes less blood to
reach tissue
• We were able to slow blood flow to
the extremities using a
sphygmomanometer
42. References
• Ahmed, Shahid, Anita K. Siddiqui, Cristina P. Sison, Rabia K. Shahid, and Joseph Mattana. "Hemoglobin Oxygen Saturation Discrepancy Using
Various Methods in Patients with Sickle Cell Vaso-occlusive Painful Crisis." European Journal of Haematology 74.4 (2005): 309-14. Print.
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• Ashley Koch, Yang Q, and Olney R.S. "American Journal of EPIDEMIOLOGY." Humane Genome Epidemiology Review. Sickle Hemoglobin (Hb
S) Allele and Sickle Cell Disease: A Huge Review. John Hopkins Hospital, 9 May 2000. Web. 18 Oct. 2012.
• Bishop, Charles W., MD, Phyllis E. Bowen, Ph. D., and S. J. Ritchey, Ph. D. "Norms for Nutritional Assessment of American Adults by Upper Arm
Anthropometry." American Journal of Clinical Nutrition 34 (1981): 2530-539. Web.
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• Conran, Nicola, Carla Franco-Penteado, and Fernando Costa. "Newer Aspects of the Pathophysiology of Sickle Cell Disease Vaso-
Occlusion." Hemoglobin 33.1 (2009): 1-16. Print.
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• "CT Scan vs MRI." - Difference and Comparison. N.p., n.d. Web. 24 Oct. 2012. <http://www.diffen.com/difference/CT_Scan_vs_MRI>.
• "Edmund Optics: USB 2.0 CMOS Machine Vision Cameras." Optics, Imaging, and Photonics Technology. Edmund Optics, n.d. Web. 23 Oct. 2012.
<http://www.edmundoptics.com/imaging/cameras/usb-cameras/eo-usb-2-0-cmos-machine-vision-cameras/2818>.
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• Eker, Charlotta. Optical Characterization of Tissue for Medical Diagnostics. Lund: n.p., 1999. Web.
<http://www.atomic.physics.lu.se/fileadmin/atomfysik/Biophotonics/PhD_Theses/PhD_Thesis_Charlotta_Eker.pdf>.
• "FLIR I3 Compact Thermal Imaging IR Camera." FLIR Systems. NeoBits, n.d. Web. 23 Oct. 2012.
<http://www.neobits.com/flir_systems_60101_0101_60101_0101_flir_i3_compact_p3946969.html?atc=gbs>.
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• Hay Willian, Katsuyuki Miyasaka, and Christian Poets. "Pulse Oxymetry Principle." Principle of Pulse Oximetry Technology. Ed. Steven Baker.
Masimo Corporation, Siemens, 10 Sept. 2010. Web. 18 Oct. 2012.
43. References
• "How Does a Pulse Oximeter Work." Http://portableoxygenconcentrator.com. POCmedical, n.d. Web. 24 Oct. 2012. <http://www.google.com/imgres?start=944>.
• Ignjatovic Nebojsa, Marina Vasiljevic, Dragan Milic, Jelena Stefanovic, Miroslav Stojanovic, Aleksandar Karanikolic, Alenksandar Zlatic, Goran Djordjevic, Sasa
Zivic, Ljiljana Jeremic, Ivona Djordjevic, and Radmilo Jankovic. "Diagnostic Importance of Pulse Oximetry in the Determination of the Stage of Chronic Arterial
Insufficiency of Lower Extremities." Diagnostic Importance of Pulse Oximetry in the Determination of the Stage of Chronic Arterial Insufficiency of Lower
Extremities (2010): 300-04. Doiserbia.nb.rs. May-June 2010. Web. 18 Oct. 2012.
• Julian L. Allen, et al. "Hypoxaemia In Sickle Cell Disease: Biomarker Modulation And Relevance To Pathophysiology." Lancet 362.9394 (2003): 1450-1455.
Academic Search Complete. Web. 21 Oct. 2012.
•
• Kamshilin, Alexei A., Serguei Miridonov, Victor Teplov, Riku Saarenheimo, and Ervin Nippolainen. "Photoplethysmographic Imaging of High Spatial
Resolution."Biomedical Optics Express 2.4 (2011): 996-1006. Web.
•
• Lonergan Gael J., David B. Cline, and Susan L. Abbondanzo. "Sickle Cell Anemia." RadioGraphics. N.p., n.d. Web. 18 Oct. 2012.
<http://radiographics.rsna.org/content/21/4/971.full>.
• Lopez, Bernard L., et al. "Pulse Oximetry in the Adult ED Patient with Sickle Cell." The American Journal of Emergency Medicine 23.4 (2005): 429-32. ProQuest
Nursing & Allied Health Source. 21 Oct. 2012 .
•
• Particular Requirements for Basic Safety and Essential Performance of Pulse Oximetry Equipment. ISO 80601-2-61:2011. Geneva, Switzerland : ISO.
•
• "Research & Screening." Sickle Cell Disease Association of America, Inc. Sickle Cell Disease Association of America, Inc., n.d. Web.
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• Schutz, Sandra L. "Oxygen Saturation Monitoring by Pulse Oximetry." American Association of Critical- Care Nurses. N.p., n.d. Web. 23 Oct. 2012.
<http://www.aacn.org/WD/Practice/Docs/ch_14_PO.pdf>.
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Notes de l'éditeur
The varying levels of oxygen concentration in the blood can be used as an indicator to determine whether or not a vaso-occlusive crisis is occurring. By using different optics techniques, such as pulse oximetry or photoplethysmography, these levels of oxygen concentration can be measured.
This device should be able to adjust to varying thicknesses.
Find a Correlation Between the Varying Levels of Oxygen Saturation in the Blood and the Level of Pain that an Individual May be ExperiencingA pain scale can be created that ranges from one to ten. Each number on the pain scale can correlate to a specific range of oxygen saturation levels.
Research shows that people diagnosed with sickle cell anemia share a similar hemoglobin-oxygenation curve as people without the disease (Figure 1).Therefore, the principles of pulse oximetry are applicable to people with sickle cell disease; the oxygen saturation measurements taken on a person with Sickle Cell Disease with a pulse oximeter should be accurate compared to people without the disease. Our group conducted three experiments mimicking a vaso-occlusive crisis to determine if oxygen saturation percentages differed during normal and vaso-occlusive conditions.
Methods of Data Collection. Vaso-occlusive crises were simulated by using a tourniquet. Different pulse oximeters were used to obtain the blood oxygen saturation percentages. These were the nanotracker, the medtroniklifepak 12 clinical pulse oximeter, and the AD Instruments MLT321 Pulse oximeters.
Table 1 shows the data collected from the photoplethysmograph otherwise known as the nanotracker. A vaso-occlusive crisis was simulated using a tourniquet; the nano tracker recorded the blood oxygen concentration during the simulation. The table shows that the standard deviation and the p values are very small. These were calculated using the built in Excel functions, and this shows that the data was significant.
Table 2 shows the data collected from the Medtronic Lifepak 12 Pulse Oximeter. This test also used a tourniquet to mimica vaso-occlusive crisis. The standard deviation and the p-values were also small for this experiment.
The third test was conducted in the same fashion as the first two, but we added a control measurement while using AD Instruments MLT321 pulse oximeters. A pulse oximeter was placed on each hand. A vaso-occlusive crisis was simulated in one arm (experimental), and the other arm remained in normal conditions (control). During the simulation, the pulse oximeters took blood oxygenation concentration readings.
T-tests were done on the sets of data within the three tables. The p-values shown were calculated using the T-Test function in Microsoft Excel.The results of the t-tests show that the O2 saturation decreased significantly when the tourniquet was placed on the arm. Therefore, it can be deduced that a pulse oximeter can detect a vaso-occlusive crisis. The pulse oximeter on the control hand read normal blood oxygenation levels while the pulse oximeter on the experimental arm read significantly lower blood oxygenation levels. By these experiments, it can be determined that a pulse oximeter can be used to detect the general location of a vaso-occlusion.
The table shown here shows an estimation for the total price of our budget. This includes the cost of producing the prototype and the cost for travel to perform immersions. Currently, there are no major competitors against our design. In some cases, a doctor can order a CT scan, which costs $1200 - $3200 (“CT Scan vs. MRI”).
Our device will utilize an adjustable arm-band design. This will allow the device to conform to different sizes and allow for ease of use. A system of multiple LEDs and detectors will be used.
The benefits of a multiple LED system is that it produces more light which allows the detector to see dark spots better. Even if the crisis occurs outside of the emitance of the LED, our detectors can identify a crisis
We have developed a technique which will incorporate two pulse oximeters. This allows us to get a baseline reading while at the same time identifying a crisis. Preliminary testing has proven this method to be viable.
Recreating a vaso-occlusive crisis was important part of our research. We were able to recreate a vaso-occlusive by using a blood pressure cuff to slow blood flow to the extremities.
Here is a table of what our proposed pain scale will look like.