Q. Our laboratory routinely does fingerstick glucose tests on a glucose
meter in the morning. Occasionally, the patient also has a basic
profile ordered, in which case the meter sugar may be canceled or,
if performed, will result in the nurses dosing the insulin from
the meter value and then receiving a serum glucose as part of the
profile. Although the meter and analyzer correlate on similar samples
(fingerstick and capillary tube obtained for serum) within 15 percent,
the values may be on opposite sides of an insulin dosage level,
which causes concern. Should the dosage always be from the meter
since that report is received quickly as a point of care, or should
the glucose be reported from only one method and the other test canceled?
A. Your question about the consequences of biases between two different
analyzers measuring the same analyte is important to laboratorians.
Much has been written about practices to minimize this issue. As
you suggest, these differences may lead to different insulin doses,
which could possibly cause a patient to suffer an adverse effect.
The introduction of bedside glucose monitoring has led laboratorians to again focus
on this subject. The issue potentially has major consequences since
about one of every seven dollars spent on health care is spent on
diabetes, and better control of diabetes results in delayed and
decreased complications for those afflicted. Almost 20 percent of
Americans will suffer from disorders of glucose metabolism during
their lifetime, and the incidence of diabetes is increasing. Therefore,
even small improvements in the care of diabetics may have significant effects.
Your question delves into many areas. First, you should be aware that the biases
between glucose measurements made using reflectance meters and plasma
glucose values made in the central laboratory are decreasing. This
is in part because some manufacturers are recalibrating their analyzers
to minimize these differences. We have seen this in some of the
CAP Q Probes studies. In my opinion, there is no valid scientific
reason for these differences to exist.1 I would suggest that laboratorians
add the phrase “minimal bias between bedside and central laboratory
glucose measurements” to their list of desired features in a bedside glucose analyzer.
Second, even though there are what we consider to be large errors made in the
measurement of glucose, far greater errors occur in the actions
taken in response to a glucose result. For example, the typical
response to elevated glucose values is to draw insulin into a syringe
and inject it into the patient. Recent research has emphasized the
imprecision of measuring the required amount of insulin, especially
for neonates, where the insulin doses are small. Some older studies
found that these errors may be as high as 100 percent and are markedly
influenced by dead spaces in the syringe or air bubbles.2 Even more
recent studies indicate that measuring insulin in a syringe prior
to injection may have a coefficient of variation of five to 33 percent.3
Errors are more frequent when a combination of insulins are prepared
for an injection than when a single insulin is used.
Others have pointed out that the effect of injected insulin is dependent on
the injection site. A common error is to inject insulin intramuscularly
rather than subcutaneously, or into scar tissue where absorption
is slow. Even when a single insulin was injected subcutaneously,
the halftime was found to be 6.9 +/– 2.6 hours, with an intraindividual
coefficient of variation of 26 percent and an interindividual coefficient
of variation of 55 percent.4
Despite these large errors in the delivery of insulin compared with the relatively
small errors in the measurement of glucose caused by biases and
imprecision, there are those rare patients who are harmed by inaccurate
glucose measurements. It is important that we continue to work to
decrease the biases between these two glucose measurements, as others
continue to work on the inaccuracies of insulin delivery.
As for your specific concern, I suspect that you will not see any complications
caused by biases between your glucose methods, as the imprecision
of insulin measurement and delivery is far greater and masks the
error of glucose measurement. I recommend that you continue your
practice of measuring glucose in the central laboratory when other
tests are ordered and not measure glucose at the bedside at these times.
J. Howanitz, MD
- Howanitz PJ, Jones BA. Bedside glucose monitoring. Comparison
of performance as studied by the College of American Pathologists’
Q-Probes program. Arch Pathol Lab Med. 1996; 120: 333–338.
- Arnott RD, Cameron MA, Stepanas TV, et al. Insulin syringes:
dangers of dead space. Med J Aust. 1982;10:39–40.
- Smith CP, Sargent MA, Wilson BP, et al. Subcutaneous or intramuscular
insulin injections. Arch Dis Child. 1991; 66: 879–882.
- Kolendorf K, Aaby P, Westergaard S, et al. Absorption, effectiveness,
and side effects of highly purified procine NPH-insulin preparations (Leo).
Eur J Clin Pharmacol. 1978;14:117–124.
Professor and Vice Chairman
Department of Pathology
SUNY Downstate Medical Center,
Chair, CAP Point of Care Testing Committee
Q. I am looking for a method to test body fluids (peritoneal, pleural)
for specific gravity. We have a refractometer in the urinalysis
laboratory, but the literature on urine specific gravity testing
says the urine refractometer should not be used to test other body
fluids. Ithink most labs use the urine refractometer for testing
other fluids even though it is calibrated for urine specimens. What
is a suitable method for handling lab requests for specific gravity
on other body fluids?
A. The urine refractometer should only be used to determine urine specific
gravity. It is optimized to urine where the solutes that contribute
to specific gravity are urea, sodium, chloride, sulfate, and phosphate.
The urine refractometer gives spurious results when pure sugar or
salt solutions are measured, and conversion tables are required
if simple salt solutions are used to check the refractometer’s calibration.
Because you ask about pleural and peritoneal fluids, I assume you plan to use
specific gravity to estimate protein concentration since the electrolyte
concentration of these fluids fairly closely mimics plasma in almost
all cases. Estimating the specific gravity of a protein containing
fluids classically requires a graded series of copper sulfate solutions
of known specific gravity. A drop of fluid is pipetted into the
solution and then a shell of protein-copper forms around the drop.
If the drop has a specific gravity greater than that of the copper
sulfate solution, it sinks to the bottom. If the specific gravity
is less than that of the copper sulfate solution, it floats to the
surface. If the specific gravity approximates that of the copper
sulfate solution, then the drop remains suspended in the solution.
I’m not sure why you would want to use this relatively rough and labor-intensive
method, however, since fluid protein levels can be measured directly by a number
of colorimetric methods on chemistry analyzers. The primary reason to measure
protein is to assist in differentiating a transudative or exudative fluid. (Cell
counts are also quite useful in this regard.) The modified criteria of Light
(Light RW, et al. Ann Intern Med. 1972; 77: 507–513) are a classic
standard for establishing the exudative nature of a fluid. They require that
the fluid-to-serum total protein ratio be greater than 0.5; the fluid-to-serum
ratio of lactate dehydrogenase activity be greater than 0.6; and the LDH activity
in the fluid be greater than two-thirds of the upper normal limit of lactate
dehydrogenase in the serum.
Robert Novak, MD
Department of Pathology
Medical Center of Akron (Ohio)
Chair, CAP Hematology/Clinical Microscopy Resource Committee