Pennsylvania Patient Safety Advisory Icodextrin in Peritoneal Dialysis Solution May Cause Falsely High Blood Glucose Readings ABSTRACT Handheld POC glucose meters provide a quick diag- nosis and afford rapid treatment. However, blood Falsely elevated blood glucose level readings can glucose readings can be falsely elevated by certain lead to incorrect treatment and, subsequently, serious substances when using glucose meters.2 Blood con- patient harm or death. Blood containing certain sac- taining levels of maltose, galactose, or xylose can react charides can falsely elevate the results obtained from with the GDH-PQQ used in some glucose monitor- point-of-care (POC) glucose meters using the glucose ing systems.3* Icodextrin, used in peritoneal dialysis dehydrogenase pyrroloquinolinequinone (GDH-PQQ) (PD) solutions, is one such substance. It is a colloidal enzyme/indicator test method. At-risk patients include osmotic agent consisting of a starch-derived, water-sol- peritoneal dialysis patients receiving dialysis solutions uble glucose polymer. It is available under the brand containing icodextrin, patients receiving certain types name Extraneal® distributed by Baxter Healthcare. of immunoglobulin therapy, or patients receiving other drugs containing maltose, galactose, or xylose. GDH- Glucose testing uses enzymes (glucose oxidase, glucose PQQ meters cannot distinguish between maltose, hexokinase, or glucose dehydrogenase) and an indica- galactose, or xylose contained in blood. Mitigation tor such as PQQ or nicotine adenine dinucleotide strategies to help facilities reduce or eliminate falsely (NAD). Glucose meters that use the GDH-PQQ- elevated readings include educating staff and at-risk enzyme test method cannot distinguish between patients about the problem and becoming familiar glucose, maltose, galactose, or xylose, while glucose with the enzymatic test methods used by POC glucose meters using the other methods listed above do not meters; labeling affected POC meters and contrain- have this limitation. dicating their use for patients receiving solutions In the report described above, the patient’s medi- containing icodextrin, maltose, galactose, or xylose; cal history included dialysis. The problem of falsely and instructing staff and at-risk patients to use POC elevated glucose levels typically affects diabetic patients meters not based on the GDH-PQQ method. receiving continuous ambulatory PD treatment. (Pa Patient Saf Advis 2008 Jun;5[2]:64-5.) Glucose-based dialysate is used in PD solutions for ultrafiltration. Ultrafiltration is the process of remov- ing fluids from the bloodstream of a kidney dialysis Blood containing maltose, galactose, or xylose can patient during PD. The glucose-based dialysate acts falsely elevate the results obtained from point-of-care as an osmotic agent, enabling water to pass across (POC) glucose meters using the glucose dehydroge- the peritoneum membrane to maintain the osmotic nase pyrroloquinolinequinone (GDH-PQQ) enzyme/ gradient, which prolongs the filtration process.5 Ultra- indicator test method to determine blood glucose lev- filtration is important for end-stage kidney disease els in patients. Falsely elevated readings can potentially patients because their own kidneys have limited or no lead to incorrect treatment and, subsequently, serious ability to eliminate excess fluid from the bloodstream.6 patient harm or death. The following report submitted Patients at risk for falsely elevated blood glucose lev- through PA-PSRS describes a dialysis patient who was els include those receiving PD solutions containing found unresponsive with an elevated blood glucose icodextrin (e.g., Extraneal), certain types of immu- level, according to a POC glucose meter. noglobulin therapy (e.g., Octagam®), or other drugs A patient . . . with a history of dialysis, presented containing maltose, galactose, or xylose. to the emergency department with nonspecific com- Falsely Elevated Blood Glucose Level Reports plaints and weakness. The patient was evaluated and in MAUDE kept overnight for observation . . . Early in the morn- ing, the patient was found to be unresponsive. The A search of the U.S. Food and Drug Administration’s patient was intubated and required cardiopulmonary (FDA’s) Manufacturer and User Device Experi- resuscitation with return of spontaneous circulation, ence (MAUDE) database using the keyword search but [the patient was] hypotensive. ACCU-CHEK terms “glucose” and “Extraneal” revealed 28 reports [blood glucose level] at that time was greater than between 2003 and 2008 describing events of falsely 180; however, the subsequent glucose [level] in the elevated blood glucose levels in patients receiving PD lab was reported to be less than 10. The patient was solutions containing Extraneal. Many of the MAUDE transferred to [the medical intensive care unit] where reports described patients with elevated blood glucose he remained in a comatose state until he ceased to levels when tested using POC glucose meters; how- breath later in the week. ever, the elevated values were not consistent with the patients’ physiologic conditions. Other reports The Reason behind Falsely Elevated Blood Glucose Levels Hypoglycemia (i.e., low blood glucose level) can be * The ACCU-CHEK brand POC glucose meter uses the GDH- a serious medical condition, but is easily treated.1 PQQ test method. Page 64 Reprinted©2008 Pennsylvania Patient Safety Authority Authority article - ©2008 Pennsylvania Patient Safety Vol. 5, No. 2—June 2008 Pennsylvania Patient Safety Advisory specifically describe patients experiencing hypogly- of the problem and methods to prevent the false read- cemic comas, some resulting in patient death, with ing from occurring. elevated glucose levels when measured using POC glu- The most common methods offered by the medical cose meters. The brand name Extraneal was employed manufacturers and FDA to prevent falsely elevated as a search term because it is more commonly referred blood glucose levels include the following: to by clinicians than the generic form of icodextrin. Labeling affected POC glucose meters to alert What the Sources Say users not to use that meter for patients receiving icodextrin (Extraneal) or other solutions contain- Medical manufacturers and FDA provide informa- ing maltose, galactose, or xylose tion about and recommendations for the problem of falsely elevated glucose levels during POC testing Educating staff and at-risk patients about the prob- (see “Public Information on Falsely Elevated Blood lem and becoming familiar with the enzymatic test Glucose Levels during POC Testing”). Manufactur- method used by the relative POC glucose meter ers of POC blood glucose meters typically provide Instructing staff and at-risk patients to use an warning information with the instructions for use alternative POC glucose meter not based on the of the meter and/or the glucose test strips on their GHD-PQQ test method during therapy with inter- respective Web sites. Baxter Healthcare also provides fering drugs warning information on Extraneal packaging inserts In addition to the methods described above to pre- and on its Web site. Most of the ACCU-CHEK series vent falsely elevated blood glucose levels, PA-PSRS POC glucose meters use the GDH-PQQ test method clinical analysts suggest that facilities also consider the to measure blood glucose levels. However, most of the following: other common brands of POC glucose meters use a Identifying patients who have received or will be test method not affected by falsely elevated glucose receiving icodextrin-, xylose-, maltose-, or galactose- levels. FDA also provides a description on its Web site containing agents Making sure POC glucose meters not based on Public Information on Falsely Elevated the GHD-PQQ method are available in areas with Blood Glucose Levels during POC Testing high-risk patients or only using laboratory glucose testing for high-risk patients Baxter Healthcare Rechecking suspected hypoglycemia with a labora- EXTRANEAL (Icodextrin) Peritoneal Dialysis tory glucose test or a POC meter not based on the Solution [full prescribing information]. GHD-PQQ method if POC blood glucose results http://www.baxter.com/products/renal/ are inconsistent with a clinical suspicion of hypo- downloads/extraneal_pi.pdf glycemic coma LifeScan Editor's Note True Glucose Results with Glucose Oxidase As of press time, Roche Diagnostics did not respond to a request to Test Methods. review this article. However, Roche does provide information about http://www.lifescan.com/pdf/hospital/ the issue of falsely elevated glucose readings in its ACCU-CHECK aw086-149.pdf product information insert and on its Web site. See the link in the section “Public Information on Falsely Elevated Blood Glucose Roche Diagnostics Levels during POC Testing.” Another industry representative par- ticipated in review of this article. Diabetes and Dialysis: Advice on Blood Glucose Strips and Patients on Peritoneal Notes Dialysis [important product information]. 1. King DA, Ericson RP, Todd NW, et al. Overestima- http://www.rochediagnostics.com.au/ tion of blood glucose due to peritoneal dialysis fluid accu-chek/ index.asp?s1=For%20 containing icodextrin [case report]. Chest 2007 Oct Medical%20Professionals&s2=Important%20 23;132(4S):696S. Product%20Information 2. Institute for Safe Medication Practices. Be aware of false U.S. Food and Drug Administration glucose results with point-of-care testing. ISMP Med Saf Alert 2005 Sep 8;10(18):1. Fatal Iatrogenic Hypoglycemia: Falsely 3. ECRI Institute. Roche-ACCU-Chek blood glucose Elevated Blood Glucose Readings with a monitoring systems: manufacturer issues safety alert to Point-of-Care Meter Due to a Maltose- remind users that drug interference may cause falsely Containing Intravenous Immune Globulin Product. high readings [action item A7779]. Health Device Alerts http://www.fda.gov/cber/safety/glucfalse.htm 2006 Oct 20. 4. Riely SG, Chess J, Donovan KL, et al. Spurious hyperg- FDA Reminders for Falsely Elevated Glucose lycaemia and icodextrin in peritoneal dialysis fluid. BMJ Readings from Use of Inappropriate Test 2003 Sep 13;327(7415):608-9. Method. 5. Baxter. Ultrafiltration fact sheet [online]. 2002 [cited http://www.fda.gov/cdrh/oivd/news/ 2008 May 13]. Available from Internet: http:// glucosefalse.html www.baxter.com/about_baxter/news_room/news_ releases/2002/ultrafiltration_factsheet.html. Vol. 5, No. 2—June 2008 Reprinted©2008 Pennsylvania Patient Safety Authority Authority article - ©2008 Pennsylvania Patient Safety Page 65 pennsylvania Patient Safety Advisory This article is reprinted from the Pennsylvania Patient Safety Advisory, Vol. 5, No. 2—June 2008. The Advisory is a publication of the Pennsylvania Patient Safety Authority, produced by ECRI Institute and ISMP under contract to the Authority as part of the Pennsylvania Patient Safety Reporting System (PA-PSRS). Copyright 2008 by the Pennsylvania Patient Safety Authority. This publication may be reprinted and distributed without restriction, provided it is printed or distributed in its entirety and without alteration. Individual articles may be reprinted in their entirety and without alteration provided the source is clearly attributed. This publication is disseminated via e-mail. To subscribe, go to https://www.papsrs.state.pa.us/ Workflow/MailingListAddition.aspx. To see other articles or issues of the Advisory, visit our Web site at http://www.psa.state.pa.us. Click on “Advisories” in the left-hand menu bar. the pennsylvania patient safety authority and its contractors The Patient Safety Authority is an independent state agency created by Act 13 of 2002, the Medical Care Availability and Reduction of Error (“Mcare”) Act. Consistent with Act 13, ECRI Institute, as contractor for the PA-PSRS program, is issuing this publication to advise medical facilities of immediate changes that can be instituted to reduce Serious Events and Incidents. For more information about the PA-PSRS program or the Patient Safety Authority, see the An Independent Agency of the Commonwealth of Pennsylvania Authority’s Web site at www.psa.state.pa.us. ECRI Institute, a nonprofit organization, dedicates itself to bringing the discipline of applied scientific research in healthcare to uncover the best approaches to improving patient care. As pioneers in this science for nearly 40 years, ECRI Institute marries experience and independence with the objectivity of evidence-based research. More than 5,000 healthcare organizations worldwide rely on ECRI Institute’s expertise in patient safety improvement, risk and quality management, and healthcare processes, devices, procedures and drug technology. The Institute for Safe Medication Practices (ISMP) is an independent, nonprofit organization dedicated solely to medication error prevention and safe medication use. ISMP provides recommendations for the safe use of medications to the healthcare community including healthcare professionals, government agencies, accrediting organizations, and consumers. ISMP’s efforts are built on a nonpunitive approach and systems-based solutions.