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Letters |
Service de biochimie, Centre Hospitalier Affilié Univ. de Québec, 1401, 18e rue Québec, Quebec G1J 1Z4, Canada
a Author for correspondence. Fax (418) 682-8000; e-mail mgbf{at}mediom.qc.ca.
To the Editor:
Bedside capillary glucose monitoring has become widespread in most hospitals. Glucose meters have been shown to provide a reasonably acceptable degree of accuracy compared with laboratory instruments when proper quality control is in place (1). However, a recent clinical case shows that such systems have limitations in hospital settings.
A 55 years-old woman was admitted to the emergency room with suspected acetaminophen overdose. She had been found lying on the floor of her apartment in an altered level of consciousness, and a bottle of acetaminophen was discovered beside her. The patient had recently been hospitalized for a period of three months for depression. She had no history of diabetes. Capillary blood glucose as measured with the Glucometer Elite (Bayer) at the emergency room showed values of 8.4, 12.8, and 9.4 mmol/L (samples taken within 2.5 h of arrival). Serum analysis in the laboratory (Vitros 700 XR) gave glucose values <1.1 mmol/L for two different samples taken during that same time interval. Because of the discrepancy between the capillary glucose meter values and the serum glucose values measured by Vitros, the patient's serum was analyzed for glucose at another laboratory by Synchron CX-3 (0.11 mmol/L), Synchron CX-5 (0.2 mmol/L), and Radiometer EML 105 (0.0 mmol/L). Her serum acetaminophen (Vitros 700 XR) was at the highly toxic concentration of 2904 µmol/L. Despite appropriate treatment, the patient died the next night.
After ruling out a glucose meter defect as the source of the
erroneously high glucose readings, acetaminophen interference was
suspected. We therefore measured glucose on heparinized venous blood
supplemented with different amounts of acetaminophen (50 µL of
aqueous solution per mL of blood). The blood samples were drawn
from healthy volunteers who were not taking any medication. Some of
these blood samples were made hypoglycemic by incubation at 37 °C
for 4 h. Confirmation of acetaminophen concentrations was done by
measurement on a Vitros 700 XR. Simultaneous measurements of venous
blood glucose was done on five different glucose
meters according to the manufacturers' instructions. Glucose
measurements were also done on whole venous blood (EML 105) and plasma
(Vitros 700 XR, Synchron CX-3, and CX-5). Results of the glucose
measurements on the Glucometer Elite (meter 1) and the Accu-chek
Advantage (meter 2) showed a positive interference that increased with
the amount of acetaminophen added (Table 1
). Maximal deviations of 4.4 and 4.5 mmol/L were seen at the
highest acetaminophen concentration. The Precision QID (meter 3)
showed a negative interference (1.0 mmol/L at the highest acetaminophen
concentration). No interferences were seen from the One Touch Profile
(meter 4), the SureStep (meter 5), and from the laboratory glucose
measuring instruments, including the EML 105. The Glucometer Elite and
the Accu-chek Advantage were used to measure a low blood glucose value
in the presence of the highest acetaminophen concentration tested
above. A positive interference of the same amplitude was again observed
(4.4 and 4.1 mmol/L, respectively), showing that the extent of the
interference varied directly and in an absolute fashion with
acetaminophen concentration, regardless of actual glucose
concentration.
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It is worth noting that the three glucose meters that showed an interference measure glucose by electrochemical methods. The reflectance methodology used in the other two glucose meters did not show such an interference. The kit inserts provided by the manufacturers of Elite and Accu-chek Advantage do not state that such interference exists. The Precision QID information package does discuss a possible negative bias. The issue of interferences from reductive compounds such as acetaminophen on electrochemical glucose sensors has been addressed before (2). Despite a 1992 report (3) on the Glucocard glucose meter (another brand name for the Bayer Elite), which identified a positive bias with acetaminophen, this issue has not been addressed in the recently published reports dealing with electrochemical glucose meters (4)(5)(6)(7)(8)(9)(10). Kit inserts should carry this information. The magnitude of the positive bias seen here with the Glucometer Elite and Accu-chek Advantage is such that the clinical management of patients suffering from acetaminophen intoxication and its complications (one being hypoglycemia) might be affected negatively.
Acknowledgments
The authors are indebted to A.G. Béland and N. Parent-Zahri for their help in the course of this work.
References
The following articles in journals at HighWire Press have cited this article:
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  K. Dungan, J. Chapman, S. S. Braithwaite, and J. Buse Glucose Measurement: Confounding Issues in Setting Targets for Inpatient Management Diabetes Care, February 1, 2007; 30(2): 403 - 409. [Full Text] [PDF]
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 J. S. Krouwer How to Improve Total Error Modeling by Accounting for Error Sources Beyond Imprecision and Bias Clin. Chem., July 1, 2001; 47(7): 1329 - 1330. [Full Text] [PDF]
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