BLOOD GLUCOSE ANALYSIS AND THE PRE-ANALYTICAL PHASE
Original Article
IMPORTANCE OF THE PRE-ANALYTICAL PHASE
IN BLOOD GLUCOSE ANALYSIS
K. Janssen, J. Delanghe
Department of Clinical Chemistry, Ghent University Hospital, Belgium
Correspondence and offprint requests to: Joris Delanghe, E-mail: Joris.Delanghe@UGent.be
ABSTRACT
Blood glucose levels are characterized by a relatively
large intra-individual biological variability due to food
intake, physical activity and the body’s homeostatic
response. Careful attention to the pre-analytical phase is
essential to ensure accurate glucose measurements. Blood
samples should be drawn in the morning after an overnight
fast. Proper sample processing after blood collection is
crucial. When fast separation of the cells is not possible,
blood should be collected into a tube containing a glucose
preservative. Glucose concentrations may also differ
according to the blood sampling site (venous, arterial or
capillary blood). Plasma and whole blood glucose values
are not interchangeable. The International Federation of
Clinical Chemistry and Laboratory Medicine recommends
reporting the glucose concentration in plasma to avoid
clinical misinterpretations irrespective of the sample type
and method of measurement. Point-of-care testing (POCT)
glucose meters are widely used by both health profession-
als and diabetic patients to monitor blood glucose levels.
However, one should take into account that the reliability
of POCT glucose measurements depends upon a variety of
factors including underlying disease, patient drug regimens
and interfering substances as well as instrument analytical
performance and user proficiency. It is recommended to
perform a laboratory blood glucose analysis if the POCT
glucose value is in the critical hypoglycaemic or hypergly-
caemic range.
Abbreviations: ADA, American Diabetes Association; CLIA,
Clinical Laboratory Improvement Amendments; CLSI, Clinical
Laboratory Standards Institute; ICU, intensive care unit; IFCC,
International Federation of Clinical Chemistry and Laboratory
Medicine; NACB, National Academy of Clinical Biochemistry;
NaF, sodium fluoride; NCCLS, National Committee on Clinical
Laboratory Standards; OGTT, oral glucose tolerance test; POCT,
point-of-care testing; SMBG, self-monitoring of blood glucose;
WHO, World Health Organization
311
Key words: blood glucose analysis, pre-analytical, point-of-care
testing
INTRODUCTION
Blood glucose analysis is the cornerstone of both the di-
agnosis and monitoring of therapy in patients with diabetes
mellitus. The current diagnostic limits of diabetes mellitus are
narrow and increase the need for reliable results to classify
individuals correctly (1). Methods for blood glucose measure-
ment exhibit a low imprecision at the diagnostic decision limits
of 7.0 mmol/L (126 mg/dL, fasting) and 11.1 mmol/L (200 mg/
dL, post glucose load). However, classification errors may occur
due to the relatively large intra-individual biological variability
(CVs of ~ 5-7%) (2). Next to physiological variability, blood
glucose analysis depends on pre-analytical conditions (fasting
or post-prandial), specimen type (whole blood, capillary or ve-
nous blood, serum or plasma), presence of a glycolytic inhibi-
tor in the collection tube as well as time from sampling until
cell separation. Careful attention to the pre-analytical phase
is essential to ensure accurate glucose measurements. Blood
glucose testing can be performed in a central laboratory or ob-
tained by point-of-care testing (POCT). Nowadays, POCT glu-
cose devices are increasingly used to complement glucose test-
ing at the central laboratory as it provides glucose results to be
immediately available to the medical staff for taking therapeu-
tically important decisions. However, the quality of POCT still
remains a concern especially in critical care settings.
In this review, we focus on the pre-analytical requirements
of blood glucose analysis and discuss the usefulness of POCT
glucose measurements.
PRE-ANALYTICAL CONSIDERATIONS
Despite their experience in diagnosis and management
of diseases, physicians often show a lack of knowledge about
the role of pre-analytical variables on clinical laboratory tests.
Moreover, since diabetic patients and diabetic educators are
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312 BLOOD GLUCOSE ANALYSIS AND THE PRE-ANALYTICAL PHASE
primarily responsible for the proper management of their con-
dition, they must be knowledgeable of the factors that might
render data invalid when specimens are collected (3).
The pre-analytical phase is an important, but often under-
estimated part of a laboratory analysis. About 46-68% of the
laboratory errors occur in the pre-analytical phase and can be
avoided (4, 5). The pre-analytical phase consists of an order for
laboratory analysis, sample collection, transport, registration,
sample processing (e.g. centrifugation) and preservation (6, 7).
All of these steps can be a source of error.
Generally, pre-analytical variables are divided into three
categories: physiological factors, factors related to specimen
collection and interferences. Physiological factors comprise
age, sex, race, circadian rhythm, season, altitude, menstrual
cycle, lifestyle and pregnancy which can all affect to a greater
or lesser extent laboratory results (6, 7).
The ultimate glucose result is usually determined by indi-
vidual biological and pre-analytical factors (8). Blood glucose
levels vary continuously according to food intake, physical
activity and the body’s homeostatic response. Besides delay
between blood sampling and processing, storage time and
temperature, centrifugation and addition of stabilizers, these
biological factors have considerable effects, which are often
underestimated (9).
Specimen types
Several studies have reported that differences between
blood glucose measurements vary according to sample type,
methodology and timing of collection (10-13). Glucose can be
measured in different matrices such as whole blood, serum or
plasma. Glucose measurements in plasma are recommended
for the diagnosis of diabetes mellitus to avoid therapeutic
misjudgements (1, 2, 14). Blood for glucose analysis should be
drawn in the morning after an overnight fast which includes no
caloric intake for at least 8 hours, during which the individual
may consume water ad libitum (2).
Proper sample processing after blood collection is im-
portant to ensure accurate measurement of plasma glucose.
This requires rapid separation of plasma after blood collection
(within minutes) (15). If this is not possible, the sample should
be collected into a tube containing a glycolytic inhibitor to at-
tenuate the rate of glycolysis. Because the commonly used gly-
colytic inhibitors (e.g. sodium fluoride) have a delayed activity,
a tube containing a glycolytic inhibitor should be placed in ice-
water immediately after blood collection and the separation
should take place within 30 minutes (8, 15).
Glucose concentrations may also differ depending on the
blood sampling site (venous, arterial or capillary) especially
when the patient is not fasting. Fasting values for venous and
capillary plasma glucose are almost identical. But during an
OGTT, capillary glucose concentrations are significantly higher
than those in venous blood (on average 1.7 mmol/L or 30 mg/
dL) (16, 17). The difference between capillary and venous blood
glucose measurements can be explained by the rate of glucose
consumption in the tissues (10).
Acta Clinica Belgica, 2010; 65-5
Glucose analysis in capillary blood is not recommended in
situations with a reduced peripheral blood flow as it may not
reflect the true physiological state. Fingerstick blood testing
must be avoided in the following situations: severe dehydration
caused by diabetic ketoacidosis or hyperglycaemic hyperosmo-
lar nonketotic state, hypotension, shock or a peripheral vascu-
lar disease (18). Furthermore, Stahl et al. investigated whether
it was possible to perform glucose analysis on capillary whole
blood for the diagnosis of diabetes mellitus in the individual
patient. Use of mathematically converted capillary glucose val-
ues instead of the recommended venous plasma values may
result in a random, unpredictable misclassification of patients
(19).
Influence of short-term venous stasis during
phlebotomy
Venous stasis from tourniquet application during phle-
botomy should be minimized. Ideally, the tourniquet should be
released as soon as the needle enters the vein and the blood
sampling time should be as short as possible. However, in rou-
tine clinical practice the tourniquet is rarely released before
the blood collection is complete to avoid vein collapse. Fur-
thermore, several concurrent causes may prolong the blood
sampling time up to 3 minutes after tourniquet fastening (e.g.
location of the appropriate venous access, collection of many
blood samples,…) (20, 21).
The venous stasis that results from extended tourniquet
placement may influence the plasma concentration of a wide
ranges of analytes depending on the length of stasis, size and
protein-binding characteristics of the analytes. Lippi et al. in-
vestigated the influence of 1- and 3-min venous stasis on the
measurement of 12 common analytes including glucose. This
study showed that 1-min stasis had no significant effect on the
plasma glucose concentration in contrast with the 3-min sta-
sis which caused a statistically significant decrease in plasma
glucose concentration. However, in scientific literature there
is inconclusive data on the effects of venous stasis on routine
laboratory testing. Nevertheless, it is advisable that the tourni-
quet application time is less than one minute to minimize the
possible effects of venous stasis (20, 21).
Reporting
Plasma and whole blood glucose are used interchangeably
despite a physiological difference in glucose concentration
(plasma > whole blood). This may lead to a clinical misinterpre-
tation of the glucose result (1, 22) due to different reference
intervals and clinical decision limits (2).
In order to avoid therapeutic misjudgements, the Interna-
tional Federation of Clinical Chemistry and Laboratory Medi-
cine (IFCC) recommends reporting the glucose concentra-
tion in plasma (unit: mmol/L). Regardless of the sample type
or measurement principle, plasma glucose better reflects the
relevant extracellular glucose concentration that cells are pre-
sented to. Moreover, plasma glucose is not influenced by hae-
matocrit. This recommendation is also valid for POCT devices
that measure glucose in whole blood (1, 23).

The IFCC advises the use of a conversion factor of 1.11 for
the conversion of a glucose concentration in whole blood to a
plasma equivalent. This adjustment factor is only applicable for
samples from the same sampling site and in the case of normal
haematocrit values (1, 23, 24). It does not apply to the calcu-
lation of venous plasma glucose concentrations from glucose
concentrations in capillary or arterial blood (1, 23). In practice,
conversion factors used in the various POCT meters differ upon
firm.
Use of glycolytic inhibitors
Plasma glucose levels are expected to be stable if plasma is
immediately separated from cells by centrifugation after blood
collection since the enzymes that metabolize glucose are in the
cellular fraction (7). However, this is difficult to achieve in rou-
tine clinical practice. Table 1 gives an overview of the influence
of different glucose stabilizers on the blood glucose concentra-
tion.
Blood samples should be kept at 0-4 °C or centrifuged im-
mediately if whole blood is used for glucose analysis (25). In
separated, non-haemolysed, sterile serum without glycolytic
inhibitors, the glucose concentration is stable for 8 hours at
25 °C and 72 hours at 4 °C (26). Since it is impractical to cen-
trifuge all laboratory glucose samples immediately, the use of
glycolytic inhibitors is necessary to attenuate the rate of gly-
colysis. Nevertheless, it should be emphasized that these glu-
cose preservatives do not totally prevent glycolysis (27).
Glucose concentrations decrease ex vivo with time in whole
blood as a result of glycolysis which leads to an unpredictable
underestimation of the true glucose concentration. The rate of
glycolysis is on average 5-7 % (~0.6 mmol/L or 10 mg/dL) per
hour (28) and is influenced by glucose concentration, tempera-
ture, white and red blood cell count, platelet count and other
factors (29). Because of the instability of glucose in blood sam-
ples, well-defined and standardized pre-analytical conditions
are essential to ensure that the measured blood glucose con-
centration reflects the real blood glucose in the patient.
In absence of glycolytic inhibitors, glucose concentration of
newborns can decrease up to 24% 1 hour after blood collec-
Table 1: Influence of different glycolytic inhibitors on glucose concentration
Sample type and glycolytic inhibitor(s)
Whole blood
Separated, non-haemolysed, sterile serum without glycolytic inhibitors
Sodium fluoride (NaF) (2.5 mg/mL of blood) with EDTA (1 mg/dL of blood) or
potassium oxalate (2 mg/dL of blood)
A mixture of NaF (2 mg/mL of blood) and mannose (2 mg/mL of blood)
Acidification of blood combined with the addition of NaF and EDTA
A mixture of 119 mmol/L NaF and 11 mmol/L glyceraldehyde (plus 21.7
mmol/L potassium oxalate)
Lithium iodoacetate (0.5 mg/mL blood) or in combination with lithium
heparin (14.3 U/mL blood).
RT= room temperature
BLOOD GLUCOSE ANALYSIS AND THE PRE-ANALYTICAL PHASE 313
tion in contrast with the 5% decline in healthy adults when
blood specimens are stored at room temperature (30). In ad-
dition, as much as 68% of glucose can be consumed in blood
samples collected without glycolytic inhibitors from neonates
and stored at room temperature for 5 hours as a result of the
high haematocrit (30).
Sodium fluoride (NaF) and lithium iodoacetate have both
been used in blood collection tubes to preserve glucose. These
reagents can be used alone or in combination with anticoagu-
lants such as EDTA, potassium oxalate, citrate or lithium hepa-
rin (2). The nominal concentration of sodium fluoride used to
inhibit glycolysis is 2.5 mg/mL of blood in combination with an
anticoagulant such as Na2EDTA (1 mg/mL of blood) or potas-
sium oxalate (2 mg/mL of blood) (7).
Although NaF is capable of preserving glucose concentra-
tion in blood, the rates of decline of glucose in the first hour
after sampling in tubes with and without fluoride are virtually
identical (28). Plasma glucose concentration decreases up to
0.5 mmol/L (9 mg/dL) over a period of 2 to 4 hours after sam-
ple collection in tubes containing NaF. After 4 hours only, the
glucose concentration will be stable for 72 hours at room tem-
perature (28). Fluoride takes approximately 3-4 hours to stabi-
lize glucose levels because it inhibits enolase which is the ninth
and penultimate step of the glycolytic pathway. The upstream
enzymes in the glycolysis pathway still continue to metabolize
glucose until substrates are consumed (31).
The combination of mannose and NaF has been suggested
to overcome this problem. Mannose is a competitive inhibitor
of the first enzyme of the glycolytic pathway (hexokinase). The
inhibitory effect of mannose is short lasting (at most 4 hours),
but in the meantime NaF has become active. A mixture of so-
dium fluoride (2 mg/mL of blood) and mannose (2 mg/mL of
blood) can be effective in minimizing the loss of glucose and
achieving a better glucose stabilization (9).
Another approach to improve blood glucose preservation is
the acidification of blood combined with the addition of NaF
Characteristics
Rate of glycolysis is 5-7% on average (~0.6 mmol/L or 10 mg/dL) per hour
Stable glucose concentration for 8 hours at 25°C and for 72 hours at 4°C
Glucose concentration decreases up to 0.5 mmol/L 2 to 4 hours after collection
After 4 hours: stable glucose concentration for 72 hours during storage at RT
Effective in minimizing the loss of glucose and achieving a better glucose
stabilization in comparison with NaF alone
Rapid inhibition of the glycolysis and more effective than NaF alone
Prevents consumption of glucose completely even after incubation for 24 hours at
RT prior to centrifugation
Optimal working 3 hours after blood sampling
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314 BLOOD GLUCOSE ANALYSIS AND THE PRE-ANALYTICAL PHASE
and EDTA. Acidification of blood with a citrate buffer inhibits
hexokinase and phosphofructokinase, early enzymes in the gly-
colytic pathway, which quickly stops glycolysis. The inhibitory
effect of acidification is sustainable for approximately 10 hours
at 25 °C which can easily be prolonged by the addition of a
small amount of NaF (31).
An alternative strategy for efficient glycolytic inhibition is
the use of glyceraldehyde in addition to fluoride. le Roux et al.
demonstrated that the best glycostatic agent is a combination
of 11 mmol/L glyceraldehyde and 119 mmol/L NaF (plus 21.7
mmol/L potassium oxalate as anticoagulant). This combination
prevents consumption of glucose completely even after incu-
bation for 24 hours at room temperature prior to centrifuga-
tion (25).
Besides NaF, lithium iodoacetate is frequently used as a
glucose preservative. It inhibits the fifth enzyme in the glyco-
lytic pathway (glyceraldehyde-3-phosphate dehydrogenase)
and can be used alone (0.5 mg/mL blood) or in combination
with lithium heparin (14.3 U/mL blood). Lithium iodoacetate
works optimal 3 hours after blood sampling (28, 32).
Interferences
Interferences (endogenous and exogenous) are factors
which may have an influence on the clinical interpretation of
laboratory data or on the measurement of an analyte. Endoge-
nous interferences are caused by substances that are present in
a patient by nature such as turbidity due to hyperlipemia, hae-
molysis,… Exogenous interferences are substances which are
present in the blood collection tubes such as anticoagulants,
stabilizing additives or substances which were administered to
the patient (e.g. drugs) (6).
1) Influence of haemolysis
Haemolysis has been defined as the release of intracellular
components from erythrocytes, thrombocytes and leukocytes
into the extracellular fluid (i.e. the plasma or serum). It can oc-
cur in-vivo as well as in-vitro during the different steps of the
pre-analytical phase. Haemolysis can be caused by inappropri-
ate blood sampling or by errors during transport, handling of
specimens and storage (7, 33).
Table 2: Advantages and disadvantages of POCT glucose measurements
POCT glucose measurements
Advantages
Minimal sample volume (1-20 μL) Adequate training of patients and medical staff
Rapid turnaround times (<30 s) Possible interferences
Limited pre-analytical phase Analytical performance
• No ex vivo glycolysis
• No transport
• No centrifugation
Calibration
CL= central laboratory
Acta Clinica Belgica, 2010; 65-5
Generally, haemolysis has little effect on analytes that are
at lower concentrations in erythrocytes than in plasma, but it
may have a substantial effect on constituents that are present
at a much higher concentration within the red blood cells than
in plasma. Therefore, it is important that doctors are aware of
the possible effects of haemolysis on the interpretation of cer-
tain laboratory tests (7, 33).
The effect of haemolysis on blood glucose analysis is unpre-
dictable due to variations in methodology and due to the mul-
tiplicity of instrumentation. Nevertheless, haemolysis should
be avoided or at least not exceed levels that would make hae-
molysis visually detectable in serum or plasma (7, 33).
2) Icodextrin interference
Most glucose dehydrogenase based methods can give false-
ly elevated glucose determinations in presence of icodextrin
metabolites. Icodextrin is a glucose polymer that is used world-
wide as an osmotic agent in continuous ambulatory peritoneal
dialysis and which can reach the blood circulation via the lym-
phatic system (34, 35). In the systemic circulation, icodextrin
is hydrolyzed to maltose, maltotriose, maltotetraose and other
oligosaccharides. These icodextrin metabolites, principally
maltose, may act as a substrate for glucose dehydrogenase
which may lead to spuriously high glucose results depending
on the specificity of the enzyme used. In contrast, glucose mea-
surements based on glucose oxidase and hexokinase systems
are not influenced by icodextrin (34).
3) Influence of oxygen
The oxygen dependency of glucose oxidase based glucose
meters may cause inaccurate glucose measurements when ox-
ygen tension varies. Glucose measurements based on glucose
dehydrogenase methods are oxygen-insensitive (36).
4) Influence of certain drugs
Ascorbic acid, acetaminophen, dopamine and mannitol can
interfere with glucose measurements performed with handheld
glucose meters. These drugs are frequently used for the treat-
ment of critically ill patients which can mask the presence of
hypoglycaemia or hyperglycaemia and may lead to inappropri-
ate insulin therapy (37).
Disadvantages
• Icodextrin
• Oxygen
• Drugs (ascorbic acid, dopamine, mannitol, …)
• No consensus about the analytical goals
• Inaccurate at very low and high glucose levels
• Influence of hematocrit
• Plasma or whole blood
• Conversion factors differ upon firm

CENTRAL LABORATORY VERSUS POCT
Blood glucose analysis can be performed in a central labo-
ratory or achieved by use of POCT glucose meters. However,
the imprecision of the current POCT glucose devices precludes
their use as a diagnostic tool for diabetes mellitus (2). Table 2
highlights the advantages and disadvantages of POCT glucose
measurements.
One of the major advantages of POCT glucose meters is their
practicality with rapid turnaround times because of the limited
pre-analytical phase (no transport, no centrifugation). Moreover
they require very small sample volumes (1-20 μL) (38).
POCT also requires an adequate training of patients and
medical staff. Skeie et al. compared the analytical perfor-
mance of five POCT glucose meters obtained by patients and
by medical laboratory technicians. These authors found that
the imprecision of the evaluated systems in the hands of pa-
tients varied from 7 to 20 %, while the imprecision varied from
2.5-5.9 % when the meters were used by lab technicians (39).
Furthermore, none of the glucose meters met the published
performance specifications proposed by the American Diabe-
tes Association (ADA) (± 10%). The performance was better
when compared with the quality specifications of the Inter-
national Organization for Standardization (ISO) which requires
that 95% of glucose measurements lie between the target ±
20%. In this study, only 86% of the blood glucose measure-
ments performed by patients fulfilled the ISO standard. The
authors stress the critical role of education in ensuring good
performance of POCT glucose meters (39). As far as training
is concerned nursing staff should be included. Adequate train-
ing of nursing staff is very difficult to organize because of high
turnover.
In practice, POCT glucose measurements often do not ful-
fil the quality goals. Bias is mainly due to the use of different
standardization and calibration techniques (whole blood versus
plasma) and great lot-to-lot variability of the different glucose
strips in comparison with the reagents used in the central lab
(24, 39, 40).
It is important that POCT results are integrated into a
laboratory information system which provides reliable glucose
results through the use of quality controls and automatic cali-
bration. Several manufacturers have introduced POCT glucose
meters with data management software which allow quali-
fied laboratory personnel to monitor instrument performance,
quality control and patient results.
Analytical performance of POCT glucose meters
Nowadays POCT glucose devices are used for taking ther-
apeutically important decisions. Therefore it is essential that
these POCT glucose meters have an acceptable analytical per-
formance over the practically relevant range of concentrations
and that their glucose results correlate well with those of labo-
ratory analyzers (18).
Numerous analytical goals have already been proposed for
the performance of glucose meters but currently there is no
BLOOD GLUCOSE ANALYSIS AND THE PRE-ANALYTICAL PHASE 315
consensus. The widely divergent criteria include expert opinion,
opinion of clinicians, legislation, state of the art and biological
variation.
In 1987, the ADA recommended for self-monitoring of
blood glucose a maximum allowable CV of 10% at glucose
concentrations of 1.7-22.2 mmol/L (30-400 mg/dL) and a max-
imum bias of 15% from a reference method value (41, 42). In
1996, the ADA revised the performance goal to 5% (43).
The Clinical Laboratory Improvement Amendments (CLIA)
’88 goal is less stringent in comparison with the ADA per-
formance criteria. Glucose results achieved by POCT devices
should be within 10% of target values or ± 0.3 mmol/L (6 mg/
dL) (2).
The National Committee on Clinical Laboratory Standards
(NCCLS) guidelines stipulate that POCT glucose results should
be within ± 20% of laboratory glucose at >5.5 mmol/L (100
mg/dL) and ± 0.83 mmol/L (15 mg/dL) of laboratory glucose
if the glucose concentration is ≤5.5 mmol/L (100 mg/dL) (44).
The new Clinical Laboratory Standards Institute (CLSI)
recommendations determine that for glucose concentrations
above 4.2 mmol/L (75 mg/dL) the discrepancy between POCT
devices and the central laboratory should be < 20%. For a glu-
cose concentration ≤ 4.2 mmol/L (75 mg/dL), the discrepancy
should not exceed 0.83 mmol/L (15 mg/dL) (45).
The National Academy of Clinical Biochemistry (NACB) has
proposed quality criteria for laboratory glucose analysis based
on intra-individual biological variation (46) with a maximum
allowable imprecision (CV) of ≤ 3.3% and a bias of ≤ 2.5% re-
sulting in a total error of ≤ 7.9% (2). However, the systematic
difference of 11% between whole blood and plasma already
exceeds the recommended allowable maximum error of 7.9%
by which incorrect specimen type may lead to a misinterpreta-
tion of the glucose result and a wrong diagnosis (1).
Impact of pre-analytical features on POCT glucose
measurements
POCT glucose meters are used to assist patients with dia-
betes in achieving and maintaining blood glucose concentra-
tions as close to those found in non-diabetic individuals. These
devices are also used in hospital settings as an alternative for
blood glucose analysis in the central laboratory.
Most of these POCT glucose systems measure the glucose
concentration directly in the plasma component of the blood
by filtering out the red blood cells. The obtained signal is cal-
ibrated to produce a result either as whole blood or plasma
glucose. Correct calibration of POCT glucose devices is one of
the most important pre-analytical factors. Many POCT glucose
meters are still calibrated to whole blood despite the IFCC rec-
ommendation that all glucose measuring devices should report
in plasma values by which the difference between the various
types of POCT glucose meters becomes even larger (1, 23).
POCT glucose devices are also inaccurate at very low and
high glucose levels. A study of Khan et al. showed that signifi-
cant biases occurred in the low and high glucose range between
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316 BLOOD GLUCOSE ANALYSIS AND THE PRE-ANALYTICAL PHASE
a POCT glucose measurement and a glucose determination in
the central lab (18). In the hypo- and hyperglycaemic range,
glucose results differed > 10% in more than 50% of the cases.
In the hypoglycaemic range, differences > 20% occurred in
57% of all cases (18). Therefore it is necessary to draw a blood
sample for the central laboratory whenever a hypoglycaemic or
hyperglycaemic reading is observed from point-of-care glucose
testing.
Moreover, haematocrit differences can significantly affect
POCT glucose measurements. Haematocrit effects are both
glucose and system dependent. At low haematocrit levels, most
POCT systems yield spurious higher glucose measurements
and conversely high haematocrit values are known to falsely
decrease POCT glucose measurements. Clinicians should be
aware of the effect of haematocrit levels on the performance
of POCT glucose devices as anaemia, polycythaemia and unex-
pected changes in haematocrit values are common in a hospi-
tal setting (47).
Use of POCT glucose meters in an outpatient setting
Self-monitoring of blood glucose (SMBG) is an impor-
tant component of diabetes therapy in order to achieve and
maintain specific glycaemic goals. Therefore, diabetic patients
should be educated in the correct use of POCT glucose meters
including quality control. Patients should also be instructed in
how to use the SMBG results to determine appropriate insulin
doses at different times of the day. Comparison between SMBG
and concurrent laboratory glucose analysis should be per-
formed at regular intervals to evaluate the accuracy of POCT
glucose results. Furthermore, a comparison between the mean
POCT glucose concentration and the HbA1c value can be used
as an internal control measure. In contrast to a hospital setting,
SMBG in ambulatory patients with diabetes is not susceptible
to errors due to haematocrit differences (2).
Use of POCT glucose meters in critical care settings
Accurate blood glucose measurements are essential to di-
agnose critically ill patients and to guide algorithmic insulin
regimens. Use of POCT glucose analyzers in a intensive care
unit (ICU) remains controversial as fingerstick glucose mea-
surements are inaccurate in those patients.
The single-centre study of Van den Berghe et al. in 2001
showed that intensive insulin therapy to maintain blood glu-
cose levels at or below 110 mg/dL reduced morbidity and mor-
tality among critically ill patients in the surgical intensive care
unit regardless of whether they had a history of diabetes. In
this study, blood glucose was frequently measured on whole
undiluted arterial blood using a blood gas analyzer in order to
maintain normoglycaemia (target glucose 80-110 mg/dL) and
to prevent adverse events related to hypoglycaemia (48).
Based on this trial, many attempts have been made to
achieve tight glycaemic control in critically ill patients with
varying results. There are raising concerns about the poten-
tially increased risk of severe hypoglycemic episodes with more
stringent glycaemic protocols and debate is ongoing regarding
the most appropriate target level for blood glucose (49, 50).
Acta Clinica Belgica, 2010; 65-5
Recently, the multinational Normoglycemia in Intensive
Care Evaluation-Survival Using Glucose Algorithm Regulation
(NICE-SUGAR) trial questioned the findings of Van den Berghe
et al. The NICE-SUGAR study showed an absolute increase in
death at 90 days and reported higher rates of severe hypogly-
cemia in the intensive-control group as compared to the con-
ventional-control group (51). Stringent glycaemic control in ICU
patients remains controversial and further studies are necessary
to unravel the goals and benefits of tight glycaemic control.
In many critical care settings blood glucose is measured us-
ing capillary blood and POCT glucose analyzers. Critchell et al.
compared fingerstick glucose measurements to simultaneously
sampled laboratory glucose in ICU patients. This study showed
that capillary blood glucose measured by fingerstick tend to
overestimate the actual blood glucose level in critically ill ICU
patients and does not meet the CLSI standard. Therefore, epi-
sodes of hypoglycaemia may be missed in ICU patients on tight
glycaemic control. This finding is important because the usual
clinical warning signs and symptoms of hypoglycaemia in ICU
patients can be masked by sedation and critical illness. Finger-
stick glucose measurements in critically ill patients should be
interpreted with caution as this type of glucose measurements
may result in episodes of undetected hypoglycaemia and inap-
propriate adjustments of insulin dose (52).
Impact of quality specifications for glucose meters
on the adjustment of insulin doses
Clinicians and patients with diabetes both use POCT glu-
cose meters to monitor blood glucose in order to improve clini-
cal outcomes. Therefore good analytical performance is crucial.
Current quality specifications for glucose meters allow results
with an error by 5-10% or more in comparison with the true
glucose concentration.
The simulation modelling study of Boyd and Bruns exam-
ined the quantitative effect of meter error on the ability to
identify the insulin dose appropriate for the true glucose con-
centration. Dosage errors occurred in 8-23% of insulin doses
when POCT devices with a total analytical error of 5% were
used. With a 10% total error criterion, 16-45% of doses were
not correct. The error rates for insulin dose errors of ≥ 4 units
with either the 5% or the 10% total error criterion were less
than 0.2% (53).
This study demonstrated that POCT glucose meters that
fulfil the current quality specifications allow a large fraction of
administered insulin doses to differ from the intended doses.
Similar simulation studies have shown that glucose meters that
achieve both a CV and bias <5-6% rarely lead to two-category
errors (≥4 units) concerning insulin doses. CV as well as bias
must be <1-1.5% to keep rates of smaller errors (≤2 units) be-
low 5% (53).
CONCLUSION
Blood glucose analysis requires careful attention in order to
ensure accurate glucose results. A number of important consid-
erations may influence glucose measurements. Blood should be
drawn preferably in the morning after an overnight fast. Proper

sample processing after blood collection is essential. Blood
samples should be collected into a tube containing a glycolytic
inhibitor when rapid separation of the cells is not possible.
Glucose concentrations may also differ depending on the
blood sampling site (venous, arterial or capillary blood). In the
fasting state, the glucose concentration in venous and capillary
whole blood is almost indistinguishable. During an OGTT, capil-
lary glucose concentrations are significant higher than venous
glucose values.
Plasma and whole blood glucose values are not inter-
changeable. The IFCC recommends reporting the glucose con-
centration in plasma using the conversion factor of 1.11. This
conversion provides consistent harmonized results which facili-
tates the classification of patients and leads to fewer therapeu-
tic misjudgements. This conversion factor is only applicable in
case of normal haematocrit values.
POCT plays an important role in monitoring blood glucose
levels in diabetic patients and remains a time-efficient method
of measuring glucose in acute situations. However, one should
take into account that the reliability of POCT glucose measure-
ments depends on a variety of factors including underlying dis-
ease, patient drug regimens and interfering substances as well
as instrument analytical performance and user proficiency.
Fingerstick measurements should be interpreted with great
caution in protocols of tight glycemic control because use of
POCT glucose meters in the ICU may lead to spurious glucose
results and misdiagnosis. It is recommended to perform a labo-
ratory blood glucose analysis if the POCT glucose value is in the
critical hypoglycaemic or hyperglycaemic range.
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