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Capillary Blood Glucose Testing at the Point of Care

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					                                                               Reference Section




                                           Capillar y Blood Glucose Testing at the Point of Care –
                                           Clinical Applications and the Evolution of Diagnostic Technologies
                                                                                                                                                         a report by
                                                                         D r s K e n t L e w a n d r o w s k i and E l i z a b e t h L e e - L e w a n d r o w s k i

                                                                              Associate Director, Clinical Laboratories, and Assistant, Department of Pathology,
                                                                                                                                   Massachusetts General Hospital



  Dr Kent Lewandrowski is Associate        Introduction                                                       glucose testing is currently a US$3.5–4 billion
Director of the Clinical Laboratories                                                                         market in the US, Europe and Japan.8
   at Massachusetts General Hospital
    and director of the point-of-care      The American Diabetes Association (ADA)
  testing programme. He is also an         estimates that more than 15 million Americans have                 In the past, questions were raised concerning the
        associate professor at Harvard
         Medical School, with research
                                           diabetes mellitus, a common chronic disorder with                  accuracy and reliability of early capillary glucose
    interests in pancreatic pathology      significant associated morbidity and mortality. More               meters in the hospital setting, but these issues have
and the evaluation of point-of-care        than five million of these patients have not been                  largely been resolved by the development of more
 technologies. Dr Lewandrowski was
     trained in anatomic and clinical      diagnosed and are unaware of their disorder. In the                sophisticated instruments. Consequently, most
       pathology at the Massachusetts      US, over 180,000 deaths per year are attributed to                 practitioners believe that capillary blood glucose
  General Hospital and has been on
                                           diabetes mellitus. Diabetics are at increased risk of              monitoring can be performed with acceptable
 the staff of the division of Clinical
       Laboratories since 1991. He is      cardiovascular disease, retinopathy, neuropathy and                accuracy by healthcare providers. However,
   responsible for directing the core      nephropathy, resulting in a per capita healthcare                  experience has shown that many modern glucose
    laboratories of the Massachusetts
         General Hospital and for the      cost of over US$10,000 per year for each patient. As               meters intended for hospital use may provide
              Department of Pathology      the American population ages, the number of                        unreliable results in specialised settings, for example
              Operations’ improvement      diabetics is expected to increase. Owing to the                    patients with high arterial oxygen (high PO2),
       programme. Dr Lewandrowski’s
      interest in point-of-care testing    enormous societal and personal impact of this                      abnormal haematocrits, hypoglycaemia (especially
  began while he was a resident at         disorder, considerable effort has been focused on                  premature infants in neonatal intensive care) and
the Massachusetts General Hospital,
where he was involved in designing
                                           the diagnosis and management of patients with                      induced hypothermia (cardiac surgery). The
   and implementing a point-of-care        diabetes mellitus.                                                 analytical performance of glucose meters for patient
    quality assurance programne. He                                                                           self-monitoring in the home is assumed but yet is less
 has published a number of articles
and chapters in the area of point-         Capillary blood glucose testing originally gained                  well established.
      of-care testing and is regularly     popularity as a means for diabetic patients to
               invited to speak on the
          management of point-of-care
                                           monitor their own glucose values and to direct                     In a recent report, Skeie, et al. evaluated five glucose
             technologies. In 2002, Dr     subsequent therapy.1,2 As the technology improved,                 meters in the hands of diabetic patients.9 None of the
         Lewandrowski founded a new        capillary glucose monitoring was widely                            meters, when used by patients, met published quality
      journal, Point-of-Care, and is its
                        Editor in Chief.   implemented in the physician office and hospital                   specifications of the ADA (+/- 10%)10 or the
                                           setting (see Table 1).3–7 By one estimate, blood                   proposed      International        Organization      for
   Dr Elizabeth Lee-Lewandrowski is
        currently an assistant to the
    Department of Pathology at the
                                           1. A Schiffin and M Belmonte, “Multiple daily self-monitoring: its essential role in long term glucose control in insulin-dependent
 Massachusetts General Hospital and           diabetic patients treated with pump and multiple subcutaneous injections”, Diabetes Care, 5, 1982, pp. 479–84.
she conducts clinical trials with the      2. R Tattersall and E Gale, “Patient self-monitoring of blood glucose and refinements of conventional insulin treatment”, Am.
diagnostics industry. She is also an
 instructor in Pathology at Harvard           J. Med., 70, 1981, pp. 177–82.
             Medical School. Dr Lee-       3. B Barr, S B Leichter and L Taylor, “Bedside capillary glucose monitoring in a general hospital”, Diabetes Care, 7, 1984,
   Lewandrowski’s research interests
                                              pp. 261–264.
are focused on point-of-care testing
      and the development of novel         4. P K Fairclough, R S Clements, D V Filer and D S H Bell, “An evaluation of patient performance of and their satisfaction
diagnostic technologies and she has           with various rapid blood glucose measurement systems”, Diabetes Care, 6, 1983, pp. 45–9.
published a number of articles and
 book chapters on the management           5. A Schiffrin, M Desrosiers and M Belmonte, “Evaluation of two methods of self blood glucose monitoring by trained insulin-
    of point-of-care testing. Dr Lee-         dependent diabetic adolescents outside the hospital”, Diabetes Care, 6, 1983, pp. 166–69.
 Lewandrowski received her PhD in
                                           6. P Kubilis, A L Rosenbloom, D Lezotte, et al., “Comparison of blood glucose testing using reagent strips with and without
   Chemistry from Brown University
     and an MPH from the Harvard              a meter (Chemstrips bG and Dextrostix/Dextrometer)”, Diabetes Care, 4, 1981, pp. 417–419.
    School of Public Health and she        7. E Lee-Lewandrowski, M Laposata, K Eschenbach, C Camooso, D Nathan, J Godine, et al., “Utilization and cost analysis
  completed a postdoctoral training
programme in Clinical Chemistry at            of bedside capillary glucose testing in a large teaching hospital: Implications for managing point-of-care testing”, The
                   Hartford Hospital.         American Journal of Medicine, 97, 1994, pp. 222–30.
                                           8. http://www.dresources.com, study #02, 4/5/02.
                                           9. S Skeie, G Thue, K Nerhus and S Sandberg, “Instruments for self-monitoring of blood glucose: comparisons of testing quality
                                              achieved by patients and a technician”, Clinical Chemistry, 48, 7, 2002, pp. 994–1,003.
1                                          10. American Diabetes Association, “Self-monitoring of blood glucose”, Diabetes Care, 19, 1996, S62–6.


                                                                               BUSINESS BRIEFING: NORTH AMERICAN PHARMACOTHERAPY 2004 – ISSUE 2
                                                       Capillar y Blood Glucose Testing at the Point of Care

Table 1: Capillary Blood Glucose                                   secretory defect), gestational diabetes or secondary
Monitoring – Clinical Settings                                     diabetes (resulting from pancreatic destruction, genetic
                                                                   defects, endocrinopathies or other disorders). Criteria
 Setting                 Application                               for the diagnosis of diabetes mellitus have been revised
 Home                    Long-term diabetes management             by an expert committee sponsored by the ADA.9
 Hospital                Short-term diabetes management            These guidelines differ from those recognised by the
                         Patient education                         World Health Organization.10–13 The new ADA
 Clinic                  Out-patient diabetes monitoring           guidelines will increase the number of newly
                         Patient education                         diagnosed diabetics by lowering the plasma glucose
 Public Health           Population-based screening                threshold (from >140 to >125mg/dl) necessary to
                                                                   fulfil the ADA diagnostic criteria.
Standardization (ISO) standard.11 Patient education
may improve on this disappointing level of                         Applications Of Capillary Blood
performance. These issues highlight the fact that                  Glucose Testing
bedside capillary glucose testing, while considered a
standard of care for routine diabetic monitoring,                  Diagnosis
continues to suffer from issues concerning test
reliability in a variety of settings.                              The utility of point-of-care testing (POCT)
                                                                   technologies in the diagnosis of diabetes is limited.
The development of capillary blood glucose meters                  Capillary glucose meters are accurate to within +/-
permitted patients and practitioners to monitor glucose            10% to 15% of a reference laboratory glucose value14
levels using a fingerstick whole blood specimen. This              and yield different values from plasma glucose
represented a radical improvement over traditional                 measurements. Inaccuracies and biases may result in
urine glucose measurements. Urine glucose testing by               misclassification of patients when these instruments
dipstick provided only a crude estimate of the blood               are used for diagnosis of diabetes and are therefore
glucose level and was totally inadequate for achieving             inappropriate for this application.
tight glycaemic control. For this reason, capillary blood
glucose monitoring has become the standard of care in              Public Health Screening
the home setting. Widespread use of capillary blood
glucose testing has created a strong incentive for                 Capillary blood glucose testing using point-of-care
manufacturers in the diagnostics industry to improve               devices has been used widely in public health
the analytical performance and ease of use of their                screening. Typically, the glucose meters are used in
technologies, leading to innovations that ultimately               conjunction with other types of testing (such as
benefit the patient.                                               cholesterol). Although no published studies
                                                                   document improved patient care resulting from the
Guidelines for the Diagnosis of                                    use of POCT in this application, screening
Diabetes Mellitus                                                  programmes with immediate referral to a primary
                                                                   care physician has obvious benefits. Highly
Diabetes mellitus may be classified as either type 1               accurate glucose values are not required since
(due to pancreatic beta cell destruction with absolute             patients who are identified by the screening
insulin deficiency), type 2 (characterised by insulin              technique will be followed up with more rigorous
resistance with relative insulin deficiency or an insulin          laboratory testing.

11. The expert committee on the diagnosis and classification of diabetes mellitus, “Report of the expert committee on the diagnosis
    and classification of diabetes mellitus”, Diabetes Care, 20, 17, 1997, pp. 1,183–197.
12. World Health Organization, Diabetes Mellitus: Report of a WHO study group, Geneva, World Health Org., 1985,
    (Tech. Rep. Ser., no. 727).
13. M Harris, R Eastman, C Cowie, K Flegal and M Eberhardt, “Comparison of diabetes diagnostic categories in the U.S.
    population according to 1997 American Diabetes Association and 1980-1985 World Health Organization diagnostic
    criteria”, Diabetes Care, 20, 12, 1997, pp. 1,859–862.
14. K Lewandrowski, R Cheek, D Nathan, J Godine, K Hurxthal, K Eschenbach, et al., “Implementation of capillary blood
    glucose monitoring in a teaching hospital and determination of program requirements to maintain quality testing”, The
    American Journal of Medicine, 93, 1992, pp. 419–26.
15. The diabetes control and complications trial research group, “The effect of intensive treatment of diabetes on the development
    and progression of long-term complications in insulin-dependent diabetes mellitus”, NEJM, 329, 14, 1993, pp. 977–986.
16. D Nathan, “Commentary: Some answers, more controversy, from UKPDS”, The Lancet, 352, 1998, pp. 832–833.
17. UK Prospective Diabetes Study (UKPDS) Group, “Intensive blood glucose control with sulphonylureas or insulin compared
    with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)”, The Lancet, 352,
    1998, pp. 837–853.                                                                                                                2


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                       Reference Section


    Patient Self-monitoring                                          practice for monitoring hospital in-patients with
                                                                     diabetes mellitus.18 The ADA, in a position
    Guidelines for the most optimal management of                    statement, determined that the modern management
    patients with diabetes mellitus have gradually                   of hospitalised patients with diabetes is often
    evolved as data from large clinical studies has                  enhanced by capillary blood glucose determinations
    become available.15–17 The Diabetic Control and                  at the bedside. The rapid availability of results can
    Complications Trial (DCCT) Research Group                        improve patient management and may shorten the
    reported on the appearance and progression of                    patient’s hospital stay, although the latter has never
    retinopathy and other complications in patients with             been documented in controlled clinical studies.
    insulin-dependent diabetes mellitus. The study
    compared patients using conventional therapy (one                Bedside capillary glucose testing was first initiated at
    or two insulin injections per day with daily self-               the Massachusetts General Hospital in 1990.
    monitoring of urine or blood glucose) with those                 Currently, more than 100 meters are utilised in the
    receiving intensive therapy (including insulin three             hospital and affiliated health centres.
    or more times per day adjusted according to the
    results of self-monitoring of the blood glucose                  The Evolution of Technology for the
    performed at least four times per day).15 In this                Management of Diabetes in
    study, intensive therapy delayed the onset and                   Hospitalised Patients
    progression of retinopathy, nephropathy and
    neuropathy in patients with type 1 diabetes mellitus.            Laboratory testing for the management of diabetic
    The United Kingdom Prospective Diabetes Study                    patients has undergone progressive stages of
    (UKPDS) compared dietary therapies with intensive                evolution. The development of urine glucose
    therapies including insulin and sulphonylureas in                dipstick methods to measure glycosuria provided a
    patients with type 2 diabetes. Intensive therapy of              technology for the management of diabetes mellitus.
    type 2 diabetes was also shown to be beneficial due              Urine dipsticks could be used in the hospital or home
    to improved outcomes relating to microvascular                   setting and provided a crude estimate of the blood
    disease.16,17 These studies have provided clear                  glucose value. Although urine dipstick methods
    evidence of the beneficial effect of intensive therapy           continue to be used in limited applications, this
    in patients with diabetes mellitus and for the role of           technology is largely obsolete for the management of
    patient self-monitoring of the capillary blood                   diabetic patients.
    glucose level in diabetic management.
                                                                     The development of first-generation hand-held,
    The availability of low-cost capillary blood glucose             battery-operated capillary blood glucose monitors
    technologies facilitates improved compliance with                was a radical improvement over the urine glucose
    intensive monitoring strategies and allows patients to           dipstick method. These early technologies provided
    become involved actively in the management of their              a quantitative blood glucose value (with an accuracy
    disease. To the extent that intensive therapy would              of +/- 20% of a reference value). However, the
    not be practical without home-use of capillary blood             devices were not easy to use, and major issues
    glucose meters, these technologies have created a                occurred with operator and instrument errors.
    significant opportunity to improve outcomes in the               Another major drawback was that there was no data
    management of diabetic patients. Although the                    management capability, necessitating manual record-
    lifetime cost of whole blood glucose monitoring                  keeping, which is notoriously difficult to manage.
    including meters and test strips is substantial, it is
    likely that reducing the morbidity and mortality of              First-generation capillary glucose meters were
    diabetes mellitus, particularly the complications of             criticised frequently from a cost-effectiveness
    retinopathy, nephropathy and neuropathy,                         perspective.7,19 A number of studies compared the
    substantially outweighs cost and improves the quality            cost of point-of-care blood glucose measurements
    of life for diabetic patients.                                   with testing in the central laboratory. In the
                                                                     literature, the range of values for the cost of the
    The Hospital Setting                                             point-of-care test varies from US$4.20 to US$13.49.
                                                                     The point-of-care technology is generally viewed as
    Over the past decade, capillary blood glucose                    being more expensive than testing in the central
    monitoring at the point of care has become standard              laboratory.19 One weakness of these analyses is that

    18. American Diabetes Association, “Bedside blood glucose monitoring in hospitals”, Diabetes Care, 20, Supplement 1,
        1997, S53.
    19. L Lewandrowski and K Lewandrowski, “Bedside capillary glucose testing in the management of patients with diabetes
        mellitus: clinical utility and relationship to patient outcomes”, Point-of-care testing, (Ed J Hicks), American Association
3       for Clinical Chemistry Press, in press.


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                                                  Capillar y Blood Glucose Testing at the Point of Care

Table 2: The Evolution of Hospital Bedside Glucose Testing Technologies

 Feature                                                                       First Gen Second Gen Third Gen*
 Hand-held device, fingerstick with good correlation to laboratory                 X         X           X
 No wipe technology                                                                          X           X
 Manual data download with basic quality control reports                                     X           X
 Operator certification with auto lock-out                                                               X
 Auto operator recertification                                                                           X
 Automated data management reports                                                                       X
 Bar code operator and patient ID                                                                        X
 Auto-bidirectional network to laboratory                                                                X
 Network technology for other POC devices                                                                X
 Intranet/Internet capability                                                                            X
 Bar coded reagents and test strips                                                                      X

*These features are available on the Abbott Precision PCX and are intended for illustrative purposes only.
Other systems from different manufacturers are available with many similar features. No endorsement of any
particular manufacturer is implied by this presentation.

Table 3: Examples of Configurations of Fourth-generation Hospital Glucose –
Point-of-care Systems

  Configurations                                                Examples
  Configuration 1
  Single multianalyte device networked on consolidated          Benchtop: Diametrics – Lifescan
  data management system. Many individual instruments           Mobile hand-held device: Abbott PCx – i STAT
  can be networked
  Configuration 2
  Multiple devices from one vendor that perform                 Devices may include capillary glucose meter,
  different tests networked on a single proprietary data        blood gases and electrolytes, coagulation, urinalysis,
  management system                                             cardiac markers and other tests: Roche Diagnostics
                                                                product line
  Configuration 3
  Same as configuration 2 except devices may come from          RALS (Remote Automated Laboratory System) data
  different vendors and may (or may not) use independent        management system with devices from various vendors
  data management systems

the calculated unit cost of POCT versus laboratory           Several manufacturers have introduced third-
testing does not take into account the efficiency            generation capillary blood glucose meters with
improvement for the nursing service of having                significantly enhanced data management software to
glucose results immediately available and integrated         monitor quality control and patient results (see Table
into the work flow of the personnel caring for the           2). Systems are configured to utilise bar-coded
patient. At any rate, the convenience of the point-of-       operator and patient identification systems and have
care format overcame issues of cost and instrument           a variety of quality assurance features. Manual
reliability when the technology was made available           downloading has been eliminated. The instruments
to hospital clinical staff.                                  can be networked via an intranet connection to a
                                                             computer in the central laboratory.
In response to the deficiencies of these early
devices and the imposition of more stringent                 Recently, fourth-generation instruments have
regulatory requirements in the US, manufacturers             become available that incorporate added features.
have progressively engineered the systems to                 The main theme of the fourth-generation devices is
eliminate sources of error and facilitate the                increased menu for POCT by consolidating
management of patient and quality control data.              platforms for capillary glucose testing, blood gases,
Second-generation instruments featured a ‘no                 electrolytes, activated clotting time and other tests
wipe’ technology that eliminated many operator               on a single platform. This development has been
errors. These devices also improved analytical               driven by a combination of clinical needs and
speed and had a rudimentary data management                  evolving market forces. Over the past decade,
software that permitted manual downloading of                bedside glucose testing was the main driver for
data to a personal computer.                                 penetration of point of care into the hospital. In          4


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                       Reference Section


    many countries, the hospital glucose testing market             (NCCLS) in 2001 for maintenance and continued
    is becoming saturated. Expansion of the test menu               development.
    permits growth into new areas in the hospital using
    the glucose testing platform as the core technology             Most of the features of third and fourth-generation
    to which other components can be added. The                     systems are not relevant to patient self-monitoring in
    consolidated systems permit multianalyte data                   the home setting. Consequently, home-use meters
    management on a single point-of-care system and                 and those designed for hospital applications have
    allow the central laboratory to monitor the                     largely diverged into separate product lines with
    distributed point-of-care programme throughout                  different requirements. Home-use meters are sold
    the hospital.                                                   over the counter in chemists and other retail
                                                                    environments as stand-alone devices differentiated
    Various configurations are available on fourth-                 mainly on cost, ease of use and other consumer-
    generation systems as shown in Table 3. These                   oriented features.
    systems permit integration of data from multiple sites
    throughout the hospital using either a ‘closed’ or              Generic meters and strips are widely available,
    ‘open’ architecture.                                            reducing cost and offering more choices for patients
                                                                    in a highly competitive market. One recent
    • Closed architecture – requires the customer to                innovation was a meter that can measure a glucose
      purchase all components from one vendor. These                value using a very small quantity of blood, which can
      systems are relatively easy to implement. In some             be derived from the forearm as opposed to the
      cases, individual components may perform poorly               capillary bed of the fingertip. The home market will
      and the hospital cannot substitute a product from             continue to expand due to the ageing of the
      an alternate vendor.                                          population in most developed countries, new criteria
                                                                    for the diagnosis of diabetes that emphasises lower
    • Open architecture – utilises a data management                glucose thresholds and expansion of the technologies
      software from one vendor and testing components               into emerging market populations.
      from either the same or other vendors. As devices
      from different vendors are compatible with the                Current approaches to managing diabetic patients
      data management software, individual testing                  require obtaining a blood sample, resulting in some
      components can be selected based on                           degree of discomfort and limitations on the frequency
      performance. However, these systems are typically             at which glucose readings can be made. Future
      more difficult and expensive to implement because             technologies may permit continuous glucose
      components may require a custom interface to the              monitoring (with the potential to improve insulin
      data management network.                                      therapy) or transcutaneous measurements that avoid
                                                                    the need to obtain a blood specimen. These
    From a customer perspective, the most desirable                 technologies are under active development and
    configuration is the open architecture model because            promise further improvements in diabetic management
    the customer is not locked in to a proprietary system           with potential benefits to patient outcomes and the
    that requires all components to be purchased from a             quality of life for diabetic patients. There are currently
    single vendor. However, closed systems may be                   two US Food and Drug Administration (FDA)-
    preferred if ease of implementation is a critical               approved continuous glucose monitoring devices
    selection criterion.                                            (CGMS): the MiniMed CGMS and the Cygnus
                                                                    Glucowatch Biographer.21 Both of these measure
    As the number of devices on the market continues                interstitial fluid glucose levels and are termed
    to expand, the problem of ‘connectivity’ in many                ‘minimally invasive’ technologies. Non-invasive
    hospitals is becoming unmanageable. In response to              devices under development utilise near-infrared and
    this growing concern, a Connectivity Industry                   far-infrared spectroscopy, radiowave impedance and
    Consortium (CIC) was formed in early 2000,                      optical rotation of polarised light. At some point in the
    comprising vendors, hospitals and individual experts            future, the glucose sensors may be linked to an insulin
    in POCT, to develop standards for a seamless                    pump that can adjust the insulin dose automatically.21■
    information exchange between point-of-care
    devices, electronic medical records and laboratory              Additional Information
    information systems.20 Recommendations of the
    CIC were transferred recently to the National                   This manuscript has been derived, in part, from the
    Committee for Clinical Laboratory Standards                     following publications:

    20. J Nichols, “The connectivity industry consortium: one year after. Symposium on connectivity standards”, Point of care, 2,
        2002, pp. 109–126.
5   21. B Deirdre and D Nathan, “Point-of-care testing for diabetes”, Point of Care, 3, 2002, pages in press.


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                                                   Capillar y Blood Glucose Testing at the Point of Care

E Lee-Lewandrowski and K Lewandrowski (1999),                  point-of-care testing”, Proceedings of the 18th
“Point-of-care testing in the management of diabetes           International Symposium on acute care and point-
mellitus: Clinical utility and relationship to patient         of-care testing, AACC/IFCC, Copenhagen DK,
outcomes”, Point-of-care testing, (Eds. C Price and J          May, 2000.
Hicks), American Association for clinical chemistry,
Washington DC, Chapter 16, pp. 319–335.                        E Lee-Lewandrowski and K Lewandrowski, “Point-of-
                                                               care capillary blood glucose testing: clinical applications and
E Lee-Lewandrowski and K Lewandrowski, “Process                the evolution of diagnostic technologies”, Proceedings of
improvement for bedside capillary glucose testing in a large   the 52nd General Assembly of the World Medical
academic medical center: the impact of new technology on       Association 2000, Edinburgh, Scotland, UK.




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