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.

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

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

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)

Vaso-Occlusion

• Most common complication of sickle cell disease

• Painful

• Can occur in arms, legs, chest, abdomen (American Family Physician 1027)

Vaso-Occlusion

• Sickled cells cannot deform to pass through small vessels

• Endothelial wall damage(Conran 4-8)

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

Pain Management

Drug Therapy

• Mild Pain : NSAIDs (acetaminophen, aspirin, ibuprofen, naproxen)

• Moderate-Severe Pain: Opioids

Pain Management

Drug Usual oral starting dosage in adults Comments and precautionsCodeine 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

Common Opioids Used to Treat Mild to Moderate Pain in Sickle Cell Disease

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.

Pain Management

Drug Oral/IM potency

Equianalgesic dosages Usual starting dosage in adults

IM Oral Oral ParenteralMorphine (Duramorph)

6* 10 mg 60 mg 15 to 30 mg every 4 hours

0.1 to 0.15 mg per kg every 3 or 4 hours

Hydromorphone (Dilaudid-Hp)

5 1.5 mg 7.5 mg 2 to 4 mg every 4 to 6 hours

1 to 2 mg every 4 to 6 hours

Meperidine (Demerol)

4 75 mg 300 mg 50 to 150 mg every 3 or 4 hours

75 to 100 mg every 3 or 4 hours

Levorphanol (Levo-Dromoran)

2 2 mg 4 mg 2 to 4 mg every 6 to 8 hours

Up to 1 mg IV 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.

Reluctance of Pain Treatment

• Narcotic addiction & tolerance

• Excessive sedation

• Respiratory depression

• ‘Drug-seeking’ behavior

• Addiction in sickle cell patients = ~3% (Yale et. al)

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

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.

Specifications

Product Specification Design Specification

1. Detecting varying levels of blood oxygen

saturation

Pulse oximetry will be used to detect the varying levels of

blood oxygen saturation. This must be able to read blood

oxygen saturation between 70% and 100% (ISO).

2. The device must be able to obtain

measurements through 5 inches of flesh

The device will be able to detect a fraction of the light that

is originally emitted into the arm. The fraction will be

determined using Beer’s Law and the optical properties of

human tissue.

3. Electrical components must be isolatedNo exposed wires will be present in the device, and the

leakage current will meet IEC standards (under 300µA).

4. Data acquisition must take less than 5 minutes

This includes the time taken to attach the device to the

patient, the time required for the device to take

measurements, and the time for the device to interpret

the measurements taken

5. ReliabilityThis device must be reliable with no false negatives. This

will follow ISO Standard 80601-2-61-2011.

6. Comfort/Ease of Use

The device should not cause any discomfort during use. It

should be easy to place on the patient and should be

easily removed

Alternative Methods

Method Specifications Met Pros Cons

Pulse Oximetry All

Non-invasive

inexpensive

easily adaptable for our use

May be time consuming to find the exact

location of the vaso-occlusion

If the occlusion is too great, a signal may not be

determined

Perfusion Index

AllNon-invasive

inexpensive

May be time consuming to find the exact

location of the vaso-occlusion

Fast Frame

“SpO2 Camera”11,3

Non-invasiveExpensive (Camera > $5002)

Only measures O2 at surface

Thermal Imaging 1,3

Non-invasive

Gives a general view of temperature in the

body

Fast data acquisition

Expensive (Camera>$10003)

Only measures temperature at surface

Can only work if vaso-occlusion causes a

temperature difference in skin

Sources: 1(Kamshillin 996-1006); 2EdmundOptics.com; 3Neo-Bits.com

Method Chosen

• Modified Pulse Oximeter

• Meets all specifications

• Low Cost

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)

Specific Aims

1. Confirm that a Vaso-Occlusive Crisis Can be Detected

–Blood Oxygen Saturation

–Pulse Oximetry

–Photoplethysmography

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

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

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.

Preliminary Results

(Figure 1adopted from Ahmed et. al.)

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

Preliminary Data

Table 1 - DATA FROM PHOTOPLETHYSMOGRAPH (NANO TRACKER)

Normal O2 Left Arm

Normal O2 Right Arm

O2--V-O Mimic Left

O2--V-O Mimic 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

n=2STDV R 0.09786n=3

p=0.0035 - Right Armp=0.0055 - Left Arm

Preliminary Data

Table 2 - DATA FROM MEDTRONIC LIFEPAK 12 PULSE OX

Normal O2 Left Arm

O2--V-O Mimic Left

Perfusion Index

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

n=3

p=0.0004

Preliminary Data

Table 3 - DATA FROM AD INSTRUMENTS PULSE OX

Normal O2 O2 Experimental

ArmO2--Experimental

Control Arm(Normal

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

STDV Exp 0.028116

n=4

p=0.0540—Control vs. Experimentalp=0.0285—Experimental (Normal Conditions) vs.

Experimental Conditions

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

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.

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.

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

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.

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.

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.

Design Specification

• Our device will utilize an adjustable arm-band design.• We will use multiple LEDs and detectors

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

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

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

Pain scale

Numbers from device Pain Scale

<0.82 9-10

.82-.86 6-8

.86-.90 4-5

.90 1-3

Cost Structure

ComponentsPer Unit

Price ($)

Price in

bulk($)

Number of

pieces in Bulk

Number of

units used

Total

Price ($)

Our Cost

($)

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

Converter280.00 1 280.00 Donated

Computer with

Software3200.00 Donated

Travel 150.00 150.00

Total Price 4007.00 527.02

Ghantt Chart