T-56

Engineering Design Specification Report

Design of a Minimally-Invasive Continuous Glucose Monitor for Critically Ill Patients

October 6, 2008

Team Members:

Elizabeth Bramblett ()

Meredith Goolsby ()

Sonya Parpart

()

Kimberly Roush ()

Advisor: Dr. Catherine Preissig

Pediatric Intensive Care Unit

Children’s Healthcare of Atlanta at Egleston

1405 Clifton Road NE

Atlanta, GA30322

770-653-6203

Project Description

Description of Design Problem:

For critically ill children, the threat of hyperglycemia is very real. Children with normal glucose levels when they are healthy can develop hyperglycemia without any warning while they are in the hospital.1 In fact, based on recent data from Children’s Healthcare of Atlanta (CHOA) and other studies, 20% of all pediatric intensive care unit (PICU) patients and 85% of all cardiac pediatric ICU (CICU) patients develop hyperglycemia.2,3,4 The trend seems to be that hyperglycemia can occur:

  • once the child has been placed on a ventilator.5
  • as a result of being placed on continuous renal replacement therapy (CRRT).
  • once the child requires vasopressors.2,3,4

Though the cause is not entirely understood and is currently of major debate and study,hyperglycemia is initially a stress response, but persists in some patients.6,7,8 It is likely due to a combination of insulin resistance, insulin deficiency, interaction of counter-regulatory hormones, and iatragenic use of pro-hyperglycemic medications used in critically ill patients.6,7,8As a result, continuous monitoring of these patients is necessary in order to treat the condition as it arises. Without immediate treatment, the patients risk impaired neurological function, ketoacidosis, coma, and poor wound healing. It has been shown that control of blood glucose levels with insulin reduces both morbidity and mortality in ICU patients who are in the ICU for at least three days.7,8

In the PICU, the standard of care for detecting hyperglycemiais to perform a blood draw every couple of hours and send this to the lab for processing.6 With multiple lab fees daily, this process is very expensive and many children must also endure a needle stick for each blood draw. There is also currently a device in trials, Medtronic’s Guardian, which is placed subcutaneously and takes readings from the interstitial fluid. However, glucose is better read from blood as that is how glucose is naturally circulated throughout the body.

Statement of Intended Purpose and Value Proposition:

The intended purpose of our project is the development of a minimally-invasive continuous glucose monitor for use in critically ill patients in intensive care units. Our product will read glucose through an IV catheter bathed in blood,which will allow for continuous readings after the initial needle stick. In order to reduce the amount of wires, tubes, and sticks a child and their parents must endure, a minimally-invasive glucose monitor would be ideal. The probes for this device will be disposable, so after the initial investment into the sensors and digital readouts, glucose monitoring becomes much less expensive than the current standard of care. The device is being created specifically for the PICU, with the hopes of monitoring for hyperglycemia in these patients, but it could also be used in CICUs and adult ICUs. Our device is superior to blood draws because it requires fewer needle sticks and less trauma to the children and is also a great reduction in cost. It is better than Medtronic’s Guardian due to its ability to monitor glucosein blood as opposed to interstitial fluid. Our device, upon successful design, would most likely become the standard of care for critically ill children and adults due to its ease of use and minimally-invasive nature.

Market Search:

  • Total ICUs in US:9 158
  • 62 academic PICUs
  • 48 CICUs
  • 48 adult ICUs
  • Current Size in US: 79,000 patients per year9
  • 1,000 total ICU admissions per year
  • 50% of patients admitted meet criteria for glucose monitoring
  • Underserved: 79,000 patients per year
  • All patients are currently monitored hourly
  • All patients requiring glucose monitoring are screened
  • Trends are not detected since no continuous monitoring system exists
  • Growth Rate (according to CHOA census for 2000-2007): 1.3% per year
  • Projected Size
  • (Current Size) * (Growth Rate) + (Underserved)
  • (79,000) * (0.013) + (79,000) = 80,027 patients
  • Market Value
  • Estimated cost of device (based on cost analysis below): $1,300
  • Value = (Projected Size) * (Cost) = (80,027) * ($1,300) = $104,269,100

End User and Environment of Use:

Since this device is designed for hospital use, the users of this device would include critical care nurses and intensivists. This device will be used exclusively in intensive care units and will not go home with the patients. It is used in conjunction with IV lines for patients who are severely ill. The hospital environment maintains a high level of sterility, so the sensor and digital readout should be able to withstand surface sterilization while the probes will be contained in sterile packaging. Though the patient is being monitored by multiple systems, this device will not be used in conjunction with any specific system, other than the IV catheter. While the patients and parents are not direct users of this device, they are affected by it. As a result, their thoughts and impressions are necessary to consider in the design.

FDA Regulatory Pathways:

The device is best classified as a Class II medical device under LJS: Catheter, Intravascular, Therapeutic, Long-term greater than 30 days. Our product is substantially equivalent to existing devices as it has the same intended use and the same technological characteristics. An example ofa device already on the market is the percutaneous, implanted, long-term intravascular catheter submitted as 510(k) and classified as Class II under LJS (Sec. 880.5970).10 However, our product will have a different implementation; therefore, submission of a 510(k) is required (see flow chart below). The submission fee for a 510(k) is currently $3,693.11 The FDA has 90 days to respond once an application is submitted, and the average time for clearance is roughly 150 days. Once a "clearance and commercialization" letter is received by the FDA, the continuous blood glucose monitor can proceed to market.12

Flow Chart: Describes the path to market a Continuous Blood Glucose Monitor. A 510(k) will be submitted to the FDA and must be approved prior to marketing the device.

Engineering Design Specifications

Customer Requirements:

This continuous blood glucose monitoring device must be able to:

  • Fit inside a catheter whose minimum size is 1.547 French (24 gauge).
  • Extend beyond the length of the catheter so that it is continually bathed in circulating blood.
  • Remain in the vein for extended periods without causing damage to the vein itself.
  • Transmit data continuously from the probe through the IV tubing to the sensor.
  • Communicate wirelessly between the sensor and the digital readout.
  • Alert PICU staff of dangerous blood glucose levels.

Engineering Characteristics:

The digital readout should be approximately 4” x 3” x 1”, keeping in mind that the smaller the device, the better. The digital LCD screen should be approximately 1.5” x 1”. Current devices weigh approximately 4 ounces; therefore our device should weigh at most 4 ounces.13The digital readout should be able to receive information from the sensor from at least 6 feet away. The probe must be able to fit in the smallest catheter, 1.547 French (24 gauge) and be able to extend past the end of the longest catheter so that it will be fully bathed in circulated blood. This would require a probe length greater than 1”. The sensor should be approximately 1” in diameter, but because it is not actually being placed in the body, the dimensions are not absolutely mandated. A smaller sensor is ideal for mounting on the IV hub.

The probe should be able to sense a wide range of glucose levels. The lowest level it should sense is 40 mg/dL and the highest level is 500 mg/dL (according to Dr. Preissig in September 2008). It would be equipped with an alarm to signal personnel in the PICU if the level dropped below 70 mg/dL or rose above 150 mg/dL. An example of a probe that would sense this is one that has a drop coating of a ferrycyanide mixture onto the surface of screen-printed carbon electrodes and then layering on glucose oxidase. This example of a glucose probe takes less than 15 seconds to respond and can sense glucose levels up to 600 mg/dL.14 All IV tubing and catheters used would be made of polyurethane. The current devices have a digital readout casing of high impact ABS/polycarbonate composite. Our device should be made of a similar high impact plastic that can withstand both standard cleaning and hospital sterilization. Sizes are similar to those used by the Medtronic Guardian Sensor.13 The sensor itself should also be cased in a high impact plastic to increase durability.

Manufacturing and Production Methods:

This device may require special manufacturing procedures as the probe requires manufacturing processes involving nanotechnology. Traditional factories may not be equipped to deal with these types of manufacturing methods. However, the glucose probe we have found is already in production at efficient manufacturing plants. This allows cost to be lower and the probes to be readily accessible. The technology of this device also requires wireless components, so the manufacturing methods must be equipped to deal with this. Standard IV tubing and catheters will be used and they require no special manufacturing procedures, only sterilization prior to use.

Sterilization and Packaging Methods:

Our probe will be sterilized using dry heat before packaging. Since the sensor and the digital readout will not be used in the body, they only have to be able to withstand sterilization by 70% ethanol,10% bleach, or 3% hydrogen peroxide. Standard cleaning would include using mild detergent, quaternary ammonia, and isopropyl alcohol.13 The probes will be packaged in sterile wrapping similar to the packaging of needles. It should be stored at room temperature and has a shelf life of 2 years. No special storage conditions are required, allowing this device to be kept in the general storage closets of the hospital.

A basic description of the device will be included so that the PICU staff will know the intended use of the product. The device is designed to fit patients with all size catheters, so a sizing chart is not necessary. It is understood that the staff already has the knowledge to place an IV and catheter and this device is designed to fit with these standard products. Since the users are already technically and medically minded, the instructions can be simple and to the point, describing assembly and basic use.

Integration with Other Products:

Our device does not directly work with other devices in the ICU. Its sizing must be compatible with the IV catheter in use, but the device is only communicating with its own digital readout. Since our device will be broadcasting a signal from the sensor to the digital readout wirelessly, we want to ensure that the frequency at which the glucose levels are transmitted does not interfere with transmissions of any other devices in the PICU.

Costs: (According to the hospital cost given by Dr. Preissig in September 2008)

  • Current Devices
  • Medtronic Guardian
  • Digital Readout Receiver with Transmitter (Sensor): $1,200
  • Probe: $35
  • Dexcom
  • All parts: $700
  • Cost to Hospital
  • Average cost for various monitoring systems = ($1,235 + $700)/2 = $967.50
  • Cost includes about 100 disposable probes and 10 sensors
  • Typical hospital discount for buying in bulk: 20%
  • Bulk purchase: 10 devices = ($967.50) * (10) * (0.8) = $7,740
  • Bulk purchase saves $1,935.
  • All hospitals should buy a maximum of 10 monitors (based on CHOA).
  • Expected cost will decrease as existing monitors are currently made by hand.
  • These devices are only used for diabetics at home, not in hospitals.
  • Since hospitals will have a high demand for this device, an automated manufacturing process is expected within the next few years for a fraction of the current cost.
  • Cost of Blood Work (based on CHOA price - Preissig 2008)
  • Patient cost: $63 per blood draw
  • Average number of glucose checks: 8 checks per day
  • Average ICU stay: 6 days
  • Total cost of ICU glucose checks nationwide:
  • (Current Size) * (Average # of glucose checks) * (Average ICU stay) * (Patient cost) = (79,000 patients) * (8 checks) * (6 days) * ($63) = $238,896,000
  • Amount Saved
  • One-time cost for hospitals in nation for the first year = (Bulk purchase) * (# of ICUs) = ($7,740) * (158 ICUs) = $1,222,920
  • Nationwide savings for the first year = (Total nationwide cost of blood work) – (One-time bulk purchase) = ($238,896,000) – ($1,222,920) = $237,673,080

Project Deliverables

Project Planning:

Correspondence with Client:

Our team plans to meet monthly with Dr. Preissig and email updates biweekly. It is our hope that this will keep her informed and hold us accountable, answering any questions we may have.

Final Deliverables:

At the end of this semester, we will be delivering a CAD drawing of our device. At this point, we will also be ordering the parts necessary to construct a functioning prototype of our glucose monitor. This will allow us to gain IRB approval to test our device in the PICU at Egleston to gather usability information. We can also gather feedback from the critical care nurses and the intensivists about our device.

Signatures

Team Members:

Elizabeth Bramblett: ______Date: ______

Meredith Goolsby: ______Date: ______

Sonya Parpart: ______Date: ______

Kimberly Roush: ______Date: ______

Advisor:

Dr. Catherine Preissig: ______Date: ______

References

  1. Vanhorebeek I, Ingles C, Van den Berghe G. Intensive Insulin Therapy in High-Risk Cardiac Surgery Patients: Evidence from the Leuven Randomized Study. Semin Thorac Cardiovasc Surg, 2006;18:309-316
  2. Yates AR, Dyke PC, Taeed R, et al. Hyperglycemia is a Marker for Poir Outcome in the Postoperative Pediatric Cardiac Patient. Pediatr Crit Care Med, 2006;7(4):351-355.
  3. Branco R, Garcia R, Piva J, Casartelli C, Seibel V, Tasker R. Glucose level and risk of mortality in pediatric septic shock. Pediatr Crit Care Med, 2005;6(4): 470-472.
  4. Preissig CM, Hansen I, Roerig P-L, Rigby MR. A protocolized approach to identify and manage hyperglycemia in a pediatric critical care unit. Pediatr Crit Care Med, 2008 (in Press).
  5. Yung M, Wilkins B, Norton L, Slater A. Glucose Control, Organ Failure, and Mortality in Pediatric Intensive Care.Pediatr Crit Care Med, 2008;9(2): 147-152.
  6. Digman C, Borto D, Nasraway SA. Hyperglycemia in the Critically Ill.Nutr Clin Care, 2005;8(2):94-101.
  7. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive Insulin Therapy in the Medical ICU. N Engl J Med, 2006;354:449-461.
  8. Van den Berghe G, Wilmer A, Milants I, et al. Intensive Insulin Therapy in Mixed Medical/Surgical Intensive Care Units. Diabetes, 2006;55:3151-3159.
  9. Frieda Online Database.* AMA Web Site. .html. Updated September 27, 2008. Accessed October 1, 2008.
  10. 510(k) Premarket Notification Database. Food and Drug Administration; 2008. 510(k)

number K895712. Updated December 15, 1989. Accessed September 28, 2008.

  1. Premarket 510(k) Review Fees. Food and Drug Administration Device Advice Web Site. Updated September 30, 2008. Accessed October 1, 2008.
  2. Bost FL. Device Regulatory Considerations. Lecture May 2008. edu/access/content/group/55088.200805/Lecture%20Slides/Medical%20Reg%20Info%205.08.pdf
  3. Technology and product Specifications. Medtronic Web Site. UK/physicians/guardian_rt_technology.html. Updated September 23, 2008. Accessed October 1, 2008.
  4. Lu BW, Chen WC. A Disposable Glucose BioSensor Based on Drop-Coating of Screen-Printed Carbon Electrodes with Nanoparticles. Journal of magnetism and magnetic Particles, 2006; 304(1):e400-e402.

*Only accessible to ICU staff

The following articles were referenced to formulate ideas:

  1. Bland DK, Fankhanel Y, Langford E, et al. Intensive Versus Modified Conventional Control of Blood Glucose Level in Medical Intensive Case Patients: A Pilot Study. American Journal of Critical Care, 2005;14(5):370-376.
  2. Jeremitsky E, Omert L, Dunham CM, Wilberger J, Rodrigues A.The Impact of Hyperglycemia on Patients with Sever Brain Injury. J Trauma,2005:58:47-50.
  3. Trence DL, Kelly JL, Hirsch IB. The Rationale and Management of Hyperglycemia for In-Patients with Cardiovascular Disease: Time for Change. J Clin Endocrinol Meab, 2003:88(6):2430-2437.
  4. Klein GW, Hojsak JM, Schmeidler J, Rapaport R. Hyperglycermia and Outcome in the Pediatric Intensive Care Unit. J Pediatrs, 2008;153:379-384.
  5. Branco RG, Tasker RC. Glycemic Level in Mechanically Ventilated Children with Bronchiolitis. Pediatr Crit Care, 2007;8(6):546-550.
  6. Clark L, Preissig C, Rigby MR, Bowyer F. Endocrine Issues in the pediatric Intensive Care Unit. Pediatr Clin N Am, 2008;55:805-833.
  7. Cochran A, Scaife ER, Hansen KW, Downey EC. Hyperglycemia and Outcomes from pediatric Traumatic Brain Injury. J Trauma, 2003;55:1035-1038.
  8. Faustino EV, Apkon M. Persisten Hyperglycemia in Critically Ill Children. J Pediatr, 2005;146:30-34.
  9. Odetola FO, Clark SJ, Freed GL, Davis B, Davis M. A national Survey of Pediatric Critical Care in the United States. Pediatrics, 2005;115:e382-e386.
  10. Pediatric Information. AmericanAcademy of Pediatrics Web Site. Updated September 2008. Accessed September 29, 2008.

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