Download Blood Glucose: Measurement in the Point-of

CE UPDATE—POINT-OF-CARE I
Frederick L. Kiechle, MD, PhD
Rhonda Ingram Main, MHSA, SH(ASCP)
Blood Glucose: Measurement in
the Point-of-Care Setting
ABSTRACT Point-of-care testing (POCT) for glucose at
the bedside or in the home or hospital is used to monitor
patients with diabetes—not to establish the diagnosis of
diabetes mellitus. Successful POCT for glucose in the
hospital requires the formation of an administrative
committee with membership from all affected areas. This
committee will evaluate and approve the specific device to be
used, determine areas within the hospital and individuals to
be trained and authorized to use the technology, and monitor
the quality assurance, quality control, and other records as
reviewed by the POCT coordinator(s). The POCT program
for glucose should be evaluated to eliminate potential preanalytical, analytical, and postanalytical errors. In the future,
radiofrequency or modem to the laboratory information
system will directly connect POC glucose devices. Moreover,
noninvasive measurement techniques will eliminate the
present requirement for skin puncture.
This is the first article in a 4-part continuing education series on point-of-care testing.
On completion of this article, the reader will be able to describe the biochemical
methods used to measure glucose at the bedside and list the preanalytical,
who have diabetes mellitus.2 Total health care
expenditures attributed to all types of diabetes in
1995 in the US were $47.9 billion.3 The financial
breakdown is shown in Figure 1. Approximately
10% of hospital inpatients have diabetes mellitus.4
Diagnosis
The diagnosis of diabetes mellitus is always established by blood glucose determinations performed
in the central laboratory.5 The diagnostic criteria
were revised by the American Diabetes Association
(ADA) in 19971 and the World Health Organization (WHO) in 1998.6 The ADA recommends
using a fasting plasma glucose level of 126 mg/dL
(7.0 mmol/L), and the oral glucose tolerance test is
limited to the diagnosis of gestational diabetes.
However, the WHO recommends using both the
fasting plasma glucose and the oral glucose tolerance test with a 2-hour plasma glucose level of 200
mg/dL (11.1 mmol/L) to establish the diagnosis of
type 1 and type 2 diabetes. The value of these 2 criteria in predicting morbidity and mortality among
patients with diabetes is under investigation.7
analytical, and postanalytical factors that can alter the glucose determination.
Monitoring at Home
From the
Department of
Clinical Pathology,
William Beaumont
Hospital,
Royal Oak, MI.
Reprint requests
to Dr Kiechle,
Department of
Clinical Pathology,
William Beaumont
Hospital,
3601 W 13 Mile Rd,
Royal Oak, MI
48073-6769; e-mail:
fkiechle@beaumont.
edu
276
Rationale for Point-of-Care Testing
The determination of the concentration of glucose
in the blood (venous, arterial, or capillary) is usually performed to diagnose or monitor diabetes
mellitus. Diabetes mellitus is a group of metabolic
diseases characterized by hyperglycemia resulting
from defects in insulin secretion, insulin action, or
both.1 In the US adult population, 11.2% have
impaired glucose tolerance, compared with 6.6%
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The Diabetes Control and Complications Trial
demonstrated that glucose control in type 1 diabetic patients reduced long-term microvascular
complications.8 Normoglycemia is recommended
for all diabetic patients and is best attained in
insulin-treated type 1 and type 2 patients by intensive insulin therapy or 3 to 4 insulin injections per
day.8-10 The dose of insulin is determined by a
blood glucose value obtained by a fingerstick capillary blood specimen analyzed on a portable glucose analyzer approved for home use by the US
administration, the authorization process for
testers, instrument verification, quality assurance
program, and procedural issues. It is recommended that all POCT programs be initially
approved and monitored by a permanent bedside
testing committee empowered by all levels of
hospital administration to make all decisions
related to POCT activities (Fig 2). This committee’s decisions are reviewed by 2 other groups
where potential problems may be resolved. The
Hospital care
52%
Physician and other
professional services
19%
Home health and
nursing home care
11%
Monitoring in the Hospital
Presciption drugs
5%
Medical durables
1%
Other
12%
Fig 1. Breakdown of health care costs associated with diabetes mellitus, 1995.
Total expenditures were estimated to be $47.9 billion in 1995, with a range from
$34.3 billion to $63.7 billion. Source: Hodgson TA, Cohen AJ. Medical care
expenditures for diabetes, its chronic complications, and its comorbidities. Prev
Med. 1999;29:173-186.
Bedside Testing Committee
4
Pathologists, Hospital Administration,
Nursing, Medical Staff, Infection Contol,
Quality Assurance Officer
Fig 2. Administrative
structure for pointof-care testing in a
hospital.
Section
In general, portable glucose devices have
improved in precision and accuracy with each
generation.14 Glucose testing using these devices
was introduced to hospitals around 1986.15 The
usual justification for the implementation of
point-of-care testing (POCT) is to decrease the
turnaround time and improve patient care. For
example, if the central laboratory provides a glucose result in 90 minutes for a patient whose intravenous insulin drip rate is changed every 60
minutes, the glucose value is of no clinical use in
the decision of whether to change the insulin drip
rate or not. In any one instance, the insulin drip
rate would have been modified 30 minutes before
the glucose value was available. In such situations,
the central laboratory needs to evaluate whether
the glucose turnaround time can be reduced to
less than 60 minutes. If this change is not possible,
a POCT program for glucose testing at the bedside
should be considered. The average turnaround
time for a POCT glucose is 5 minutes.16 In this
example, improved glucose turnaround time by
the central laboratory or by POCT would improve
patient outcomes by potentially reducing the time
the patient receives an intravenous insulin drip
and perhaps shortening the patient’s hospital stay.
In 1994, the National Committee for Clinical
Laboratory Standards published C30-A, which
defines a template for establishing a glucose
POCT program in a hospital.5 The guidelines
cover appropriate use of bedside glucose testing,
Scientific Communications
Food and Drug Administration (FDA).11 These
methods are classified as “waived” by the federal
law described by the Health Care Financing
Administration in the Clinical Laboratory
Improvement Amendments of 1988.11 These
portable blood glucose analyzers replaced urinary
glucose as the recommended method for monitoring the treatment of diabetic patients.1 In
spite of these recommendations, approximately
20% of patients with either type 1 or type 2 diabetes mellitus who used insulin in Tayside, Scotland, did not perform self-monitoring of blood
glucose at all.12 Outpatients with type 2 diabetes
taking oral antidiabetic medications do not benefit from home glucose monitoring, and this measurement can be reserved for the documentation
of hypoglycemia.13
Medical Care Evaluation
Committee
Departmental Representatives, Hospital
Administration, Medical Administration,
Nursing Administration
Medical Executive Committee
Departmental Chairman, Hospital Administration, Board of Trustees Member
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bedside testing committee makes decisions
related to choice of instrumentation and connectivity, location of POCT programs, compliance,
and POCT program-inspection issues.
It seems intuitive that the number of glucose
procedures in the central laboratory should
decrease after the introduction of a POCT glucose
program. However, 2 different studies reported an
increase of 10%4 and 18%17 in the number of glucose tests performed in the central laboratory after
a POCT program was established. Because patient
census and acuity were similar, the reason for this
increase in glucose testing after POCT implementation is not clear.4,17
Hospitalized patients with type 1 and type 2
diabetes are usually treated with a sliding-scale
insulin dose (insulin dose determined by recent
glucose value), given 4 times a day and requiring 4
Fig 3. Biochemical
reactions typically
used to measure
blood glucose values
with point-of-care
devices are shown. A,
Glucose oxidase
method; B, Glucose
dehydrogenase
method; and C,
Hexokinase method.
ADP, adenosine
diphosphate; ATP,
adenosine
triphosphate; NAD+,
oxidized
nicotinamide adenine
dinucleotide; NADH,
reduced NAD;
NADP+, oxidized
nicotinamide-adenine
dinucleotide
phosphate; NADPH,
reduced NADP.
fingerstick (or other) glucose measurements prior
to giving the insulin doses, followed by a meal or
snack. Many hospital laboratories find it difficult
to adjust the phlebotomy schedule around food
delivery. At our institution (William Beaumont
Hospital, Royal Oak, MI), failure to complete a
glucose determination and make the result available to a 21-bed diabetic unit 26% of the time
resulted in annual external failure costs of $45,100
(nurse, 16 minutes per event; nursing assistant, 4
minutes per event).16
Queale and colleagues18 question the value of
sliding-scale insulin with multiple glucose measurements in hospitalized patients with type 2
diabetes. They found the rate of hypoglycemia
and hyperglycemia higher in patients receiving
sliding-scale insulin compared with type 2 diabetic patients treated without a pharmacological
Glucose Oxidase
Glucose oxidase
Glucose + H2O + O2
Gluconic acid + 2H2O2
Colorimetric second reaction
Reduced chromogen + H2O2
Peroxidase
Oxidized chromogen + H2O
Electrochemical second reaction
H2O2→ 2H+ + O2 + 2e–
Glucose Dehydrogenase
Glucose
Glucose dehydrogenase
NAD+
D-glucono-delta-lactone
NADH + H+
Hexokinase
Glucose + ATP
Hexokinase
Glucose-6-phospate
Glucose-6-phospate
dehydrogenase
NADP+
or NAD+
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Glucose-6-phosphate + ADP
NADPH + H+
or NADH
6-phosphogluconate
regimen. They concluded that sliding-scale
insulin with or without a standing dose of intermediate-acting insulin was of no benefit in hospitalized type 2 diabetic patients. The impact of this
study may result in a reduction in capillary blood
glucose determinations in hospitals. However,
sliding-scale insulin treatment for inpatients are
still used in most hospitals today.
Technology
The 3 primary biochemical reactions used to measure blood glucose with POCT devices are shown
in Figure 3.19 The majority of methods require a
drop or more of fingerstick blood and do not lyse
the RBC. Because the water content of circulating
cells is lower than that of plasma (73% vs 93%),
plasma glucose values will be higher than whole
blood glucose by approximately 12% when the
hematocrit is normal. Most POCT glucose methods measure plasma glucose and not whole blood
glucose and, therefore, will be affected by hematocrit extremes. The HemoCue method (HemoCue, Mission Viejo, CA) is one of the only POCT
glucose techniques that lyse RBC. Saponin is the
lysing agent. The newer POCT glucose devices are
calibrated to plasma rather than to whole blood.20
It is important to know how the POCT glucose
device is calibrated by the manufacturer prior to
its evaluation in the laboratory.
Table 1 outlines preanalytical, analytical, and
postanalytical factors that can alter the glucose
result when a POCT device is used. If the measurement is to be made in the emergency department or intensive care unit, the patient’s systolic
blood pressure must be greater than 80 mm Hg.21
In hypotension, the blood circulating in the
extremities is shunted to the major organs of the
body. Therefore, during a hypotensive episode, a
fingerstick puncture will yield interstitial fluid and
very little capillary blood, and the glucose concentration will be underestimated. The specimen type
is also important. For example, for some glucose
oxidase methods,22 arterial whole blood will yield
values that are 30 mg/dL (1.7 mmol/L) (mean difference) higher compared with arterial serum glucose. Thirty-one of 50 patients in this study would
Table 1. Variables That Can Alter Point-of-Care Testing Blood Glucose Results
Arterial vs venous or capillary blood
Scientific Communications
Preanalytical factors
Inadequate instrument cleaning
Incorrect quality control or proficiency testing procedures
Sweat or body temperature extremes
Systolic blood pressure <80 mm Hg
Analytical factors
Glucose extremes
Hematocrit extremes
4
Improper technique
Section
Incorrect match between glucose monitor calibration and test
strip calibration
Intravenous dopamine
Low total protein
Oxygenation status (pO2)
Postanalytical factor
Data entry errors
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280
have received an incorrect insulin dose if the arterial whole blood glucose values had been used.22
One noninvasive POCT method extracts glucose
through the skin using reverse iontophoresis stimulated by an electrical potential.23,24 Glucose is
measured in the interstitial fluid by an electrochemical glucose oxidase method. Each measurement cycle requires 20 minutes to complete. The
measured interstitial glucose value lags behind the
serum glucose concentration by about 18 minutes,
secondary to the time required for a change in
serum glucose to equilibrate with the interstitial
fluid.23 Sweat on the skin will dilute the collection
fluid. Sweat and/or elevated body temperature will
initiate a skipped measurement cycle.23
The FDA accumulated over 400 medical device
reports on blood glucose monitors used in hospitals over 2 years.25 The 4 most frequent errors
reported included 2 preanalytical errors (inadequate instrument cleaning; incorrect quality control or proficiency testing procedures) and 2
analytical errors (improper technique; an incorrect match between the glucose monitor for calibration and test strip calibration when required by
the manufacturer). Some of these errors could be
eliminated if greater computer functionality on
the glucose device was available. For example, a
system lock out when quality control procedures
are not followed would require a repetition of the
quality control measurement before the operator
could proceed to patient testing.
Analytical factors include potential drug interferences. Glucose oxidase has a longer list of
potential drug interactions than does glucose
dehydrogenase.26 For example, the glucose measurements based on the glucose oxidase reaction
can be inhibited by dopamine.27 Some POCT glucose devices are affected by hematocrit extremes,
In those cases, anemia will falsely elevate and polycythemia will falsely decrease POCT glucose values. As a rule, for each change in hematocrit of
10%, there is a change in the opposite direction of
blood glucose of 3.6 mg/dL (0.2 mmol/L).28 Newborns have hematocrits of 45% (0.45) or higher
and frequently are hypoglycemic (<35 mg/dL [1.9
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mmol/L]) in the first hours of life.29 Manufacturers usually apply to the FDA for “neonatal use”
designation for their POCT glucose devices. There
is a specific need in this clinical setting for a device
that measures glucose, with precision and accuracy between 0 and 120 mg/dL (0 and 6.7
mmol/L), with elevated hematocrits. This product
would be of great value in the newborn nursery
and neonatal intensive care unit. In general, the
range of linearity of POCT glucose devices has
increased with newer generations.14
The glucose oxidase reaction requires oxygen
(Fig 3). Some glucose oxidase methods are altered
by the patient’s pO2,30-32 while other methods are
not.33 A glucose sensor using glucose oxidase and
the ferricyan ion underestimates glucose values
under high O2 administration. This effect reaches
a plateau of –21 mg/dL (–1.2 mmol/L) at 150 mm
Hg of pO2. Values of pO2 less than 50 mm Hg had
little effect.30 Kurahashi and colleagues31 developed
an equation for correcting bedside glucose values
for the patient’s pO2. Because glucose dehydrogenase is oxygen insensitive, this method provides an
accurate POCT glucose method for all blood specimen types: arterial, venous, and capillary.32
During coronary artery bypass surgery,
patients are placed on extracorporeal circulation,
which is associated with a sudden decrease in the
hematocrit and total protein secondary to hemodilution.34 Using the Reflotron (Boehringer
Mannheim, Indianapolis, IN) to monitor glucose
during this procedure demonstrated a 63 mg/dL
(3.5 mmol/L) positive bias at total serum protein
concentrations of less than 4.0 g/dL (40 g/L) and a
slight positive bias with low hematocrits.35 This
overestimation of blood glucose is attributed to an
increased volume of “plasma” separated from the
cellular elements on the glucose strip in the open
heart patients’ specimens compared with specimens from individuals who are not hemodiluted.
Table 2. Noninvasive Blood Glucose Monitoring Techniques
Vigilance and attention to preanalytical and analytical factors is critical to a successful launch of a
POCT glucose program.
The majority of postanalytical errors occur
during data entry. There are 5 POCT glucose
devices that may be purchased with management
software.36,37 However, the data must be entered
to be evaluated. These products may track entry
errors. The data management units may be interfaced to the laboratory information system (LIS)
or hospital information system (HIS); however,
this is not commonly done. The recovery of
patient results performed by POCT is awaiting a
connectivity solution in the future.
Technology Advances
for the Near Future
Data Management
Fluid extraction technology
Fluid extraction from skin
Interstitial fluid harvesting
Radiation technology
Far-infrared radiation
spectroscopy
Near-infrared diffuse reflectance
spectroscopy
Near-infrared transmission
spectroscopy
Optical rotation of polarized light
Photoacoustic spectroscopy
Radio wave impedance
Raman measurements
indwelling intravenous catheter with a glucose
sensor located on its tip.44 The availability of a
device for rapidly assessing glucose concentration
without skin puncture by retinal or corneal glucose measurement or skin transillumination will
revolutionize monitoring of glucose at home and
in the hospital.l
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A variety of noninvasive blood glucose monitoring techniques are currently under evaluation23,24,39-43 (Table 2). However, none of them
are commercially available at this time. Noninvasive methods will permit real-time bedside glucose
monitoring without the requirement of an
Utilization and cost analysis of bedside capillary glucose testing
in a large teaching hospital: implications for managing point of
care testing. Am J Med. 1994;97:222-230.
5. NCCLS. Guidelines for Ancillary (Bedside) Blood Glucose
Testing in Acute and Chronic Care Facilities; C30-A. Wayne,
Pa: NCCLS; 1994.
6. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications, I: diagnosis
and classification of diabetes mellitus provisional report of a
WHO consultation. Diabet Med. 1998;15:539-553.
7. Davies M. New diagnostic criteria for diabetes: are they
doing what they should? Lancet. 1999;354:610-611.
8. 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. N Engl J Med.
1993;329:977-986.
Section
Noninvasive Glucose Measurement
Scientific Communications
The availability of a method to capture all POCT
results and send them via an interface to the LIS or
HIS is the POCT’s “last frontier.” The events must
be handled out of the sequence most LIS/HIS systems demand. In the POCT environment, the
sequence may be patient registered, test performed, test result verified, test ordered with Acknowledgment
accession number assignment, result placed in The authors thank Pat Schmidt for preparing the manuscript.
patient’s record, and charge code generated. This
POCT sequence of events provides only 2 steps for References
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