Abstract

Falsely elevated blood glucose level readings can lead to incorrect treatment and, subsequently, serious patient harm or death. Blood containing certain saccharides can falsely elevate the results obtained from point-of-care (POC) glucose meters using the glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) enzyme/indicator test method. At-risk patients include peritoneal dialysis patients receiving dialysis solutions containing icodextrin, patients receiving certain types of immunoglobulin therapy, or patients receiving other drugs containing maltose, galactose, or xylose. GDH-PQQ meters cannot distinguish between maltose, galactose, or xylose contained in blood. Mitigation strategies to help facilities reduce or eliminate falsely elevated readings include educating staff and at-risk patients about the problem and becoming familiar with the enzymatic test methods used by POC glucose meters; labeling affected POC meters and contraindicating their use for patients receiving solutions containing icodextrin, maltose, galactose, or xylose; and instructing staff and at-risk patients to use POC meters not based on the GDH-PQQ method.

Introduction  

Blood containing maltose, galactose, or xylose can falsely elevate the results obtained from point-of-care (POC) glucose meters using the glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) enzyme/indicator test method to determine blood glucose levels in patients. Falsely elevated readings can potentially lead to incorrect treatment and, subsequently, serious patient harm or death. The following report submitted through PA-PSRS describes a dialysis patient who was found unresponsive with an elevated blood glucose level, according to a POC glucose meter.

A patient . . . with a history of dialysis, presented to the emergency department with nonspecific complaints and weakness. The patient was evaluated and kept overnight for observation . . . Early in the morning, the patient was found to be unresponsive. The patient was intubated and required cardiopulmonary resuscitation with return of spontaneous circulation, but [the patient was] hypotensive. ACCU-CHEK [blood glucose level] at that time was greater than 180; however, the subsequent glucose [level] in the lab was reported to be less than 10. The patient was transferred to [the medical intensive care unit] where he remained in a comatose state until he ceased to breath later in the week.

The Reason behind Falsely Elevated Blood Glucose Levels

Hypoglycemia (i.e., low blood glucose level) can be a serious medical condition, but is easily treated.¹ Handheld POC glucose meters provide a quick diagnosis and afford rapid treatment. However, blood glucose readings can be falsely elevated by certain substances when using glucose meters.² Blood containing levels of maltose, galactose, or xylose can react with the GDH-PQQ used in some glucose monitoring systems.³* Icodextrin, used in peritoneal dialysis (PD) solutions, is one such substance. It is a colloidal osmotic agent consisting of a starch-derived, water-soluble glucose polymer. It is available under the brand name Extraneal^® distributed by Baxter Healthcare.

Glucose testing uses enzymes (glucose oxidase, glucose hexokinase, or glucose dehydrogenase) and an indicator such as PQQ or nicotine adenine dinucleotide (NAD). Glucose meters that use the GDH-PQQ-enzyme test method cannot distinguish between glucose, maltose, galactose, or xylose, while glucose meters using the other methods listed above do not have this limitation.

In the report described above, the patient’s medical history included dialysis. The problem of falsely elevated glucose levels typically affects diabetic patients receiving continuous ambulatory PD treatment. Glucose- based dialysate is used in PD solutions for ultrafiltration. Ultrafiltration is the process of removing fluids from the bloodstream of a kidney dialysis patient during PD. The glucose-based dialysate acts as an osmotic agent, enabling water to pass across the peritoneum membrane to maintain the osmotic gradient, which prolongs the filtration process.⁵ Ultrafiltration is important for end-stage kidney disease patients because their own kidneys have limited or no ability to eliminate excess fluid from the bloodstream.⁶

Patients at risk for falsely elevated blood glucose levels include those receiving PD solutions containing icodextrin (e.g., Extraneal), certain types of immunoglobulin therapy (e.g., Octagam^®), or other drugs containing maltose, galactose, or xylose.

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* The ACCU-CHEK brand POC glucose meter uses the GDH-PQQ test method.

Falsely Elevated Blood Glucose Level Reports in MAUDE

A search of the U.S. Food and Drug Administration’s (FDA’s) Manufacturer and User Device Experience (MAUDE) database using the keyword search terms “glucose” and “Extraneal” revealed 28 reports between 2003 and 2008 describing events of falsely elevated blood glucose levels in patients receiving PD solutions containing Extraneal. Many of the MAUDE reports described patients with elevated blood glucose levels when tested using POC glucose meters; however, the elevated values were not consistent with the patients’ physiologic conditions. Other reports specifically describe patients experiencing hypoglycemic comas, some resulting in patient death, with elevated glucose levels when measured using POC glucose meters. The brand name Extraneal was employed as a search term because it is more commonly referred to by clinicians than the generic form of icodextrin.

What the Sources Say

Medical manufacturers and FDA provide information about and recommendations for the problem of falsely elevated glucose levels during POC testing (see “Public Information on Falsely Elevated Blood Glucose Levels during POC Testing”). Manufacturers of POC blood glucose meters typically provide warning information with the instructions for use of the meter and/or the glucose test strips on their respective Web sites. Baxter Healthcare also provides warning information on Extraneal packaging inserts and on its Web site. Most of the ACCU-CHEK series POC glucose meters use the GDH-PQQ test method to measure blood glucose levels. However, most of the other common brands of POC glucose meters use a test method not affected by falsely elevated glucose levels. FDA also provides a description on its Web site of the problem and methods to prevent the false reading from occurring.

The most common methods offered by the medical manufacturers and FDA to prevent falsely elevated blood glucose levels include the following:

• Labeling affected POC glucose meters to alert users not to use that meter for patients receiving icodextrin (Extraneal) or other solutions containing maltose, galactose, or xylose
• Educating staff and at-risk patients about the problem and becoming familiar with the enzymatic test method used by the relative POC glucose meter
• Instructing staff and at-risk patients to use an alternative POC glucose meter not based on the GHD-PQQ test method during therapy with interfering drugs

In addition to the methods described above to prevent falsely elevated blood glucose levels, PA-PSRS clinical analysts suggest that facilities also consider the following:

• Identifying patients who have received or will be receiving icodextrin-, xylose-, maltose-, or galactose-containing agents
• Making sure POC glucose meters not based on the GHD-PQQ method are available in areas with high-risk patients or only using laboratory glucose testing for high-risk patients
• Rechecking suspected hypoglycemia with a laboratory glucose test or a POC meter not based on the GHD-PQQ method if POC blood glucose results are inconsistent with a clinical suspicion of hypoglycemic coma

Editor's Note

As of press time, Roche Diagnostics did not respond to a request to review this article. However, Roche does provide information about the issue of falsely elevated glucose readings in its ACCU-CHECK product information insert and on its Web site. See the link in the section “Public Information on Falsely Elevated Blood Glucose Levels during POC Testing.” Another industry representative participated in review of this article.

Notes

1. King DA, Ericson RP, Todd NW, et al. Overestimation of blood glucose due to peritoneal dialysis fluid containing icodextrin [case report]. Chest 2007 Oct 23;132 (4S):696S.
2. Institute for Safe Medication Practices. Be aware of false glucose results with point- of-care testing. ISMP Med Saf Alert 2005 Sep 8;10(18):1.
3. ECRI Institute. Roche-ACCU-Chek blood glucose monitoring systems: manufacturer issues safety alert to remind users that drug interference may cause falsely high readings [action item A7779]. Health Device Alerts 2006 Oct 20.
4. Riely SG, Chess J, Donovan KL, et al. Spurious hyperglycaemia and icodextrin in peritoneal dialysis fluid. BMJ 2003 Sep 13;327(7415):608-9.
5. Baxter. Ultrafiltration fact sheet [online]. 2002 [cited 2008 May 13]. Available from Internet: http://www.baxter.com/about_baxter/news_room/news_releases/2002/ultrafiltration_factsheet.html.