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Timely Hospital Glucose Measurement: Here Today, Gone Tomorrow?

Published:September 06, 2014DOI:https://doi.org/10.1016/j.mayocp.2014.08.005
      Blood glucose meters (BGMs), first introduced in the US market in the 1970s, have revolutionized the care of patients with diabetes. Improved glucose control, enabled by frequent measurement, has greatly reduced long-term cardiovascular, renal, and ophthalmic complications. Although these devices were originally designed for and approved by the Food and Drug Administration (FDA) for “OTC self-monitoring by lay-persons,”

      Food and Drug Administration. Blood glucose monitoring test systems for prescription point-of-care use: draft guidance for industry and Food and Drug Administration staff. January 7, 2014. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM380325.pdf. Accessed July 28, 2014.

      they have ubiquitously migrated into the hospital environment in which they have become the mainstay for inpatient glucose testing. Approximately 500 million of these tests are performed per year in US hospitals.
      The increase in hospital point-of-care (POC) testing is the result of 4 major phenomena: (1) the move toward tight glycemic control (TGC); (2) the emergence of rapid, easy-to-use, and inexpensive BGMs that require a small finger-stick–derived sample of whole blood; (3) the progressive improvement in the accuracy of these devices; and (4) the increased prevalence of patients with diabetes.
      Point-of-care BGMs for hospitalized critically ill patients are now at risk because of new enforcement policies proposed by the Centers for Medicare & Medicaid Services (CMS) prohibiting the off-label use of these devices. As the CMS attempts to protect patients from this technology, which has not been appropriately tested to FDA standards, such enforcement will eliminate this important tool and no adequate replacement technology currently exists. The result will be a CMS-mandated significant decline in the quality of care for diabetes patients in the United States. Here, we describe why POC BGMs are used in critically ill patients, how they have been regulated, how they are about to be regulated, and what can be done to safely transition from inadequate documentation to proper documentation of the performance of this tool.

      Standards of Care for TGC

      In 2001, Van den Berghe et al
      • Van den Berghe G.
      • Wouters P.
      • Weekers F.
      • et al.
      Intensive insulin therapy in critically ill patients.
      reported that TGC targeting a blood glucose level of 80 to 110 mg/dL (to convert to mmol/L, multiply by 0.0259) using intensive insulin therapy significantly decreased mortality and morbidity in critically ill surgical patients. This report led to increased adoption of POC BGMs in hospitals. Tight glycemic control was applied in various settings, including the intensive care unit (ICU), operating rooms, and emergency departments as well as general care wards. The enthusiasm for TGC was tempered by the NICE-SUGAR study
      • Finfer S.
      • Liu B.
      • Chittock D.R.
      • et al.
      NICE-SUGAR Study Investigators
      Hypoglycemia and risk of death in critically ill patients.
      and subsequent studies of TGC that mostly failed to prove that TGC is beneficial.
      • Murad M.H.
      • Coburn J.A.
      • Coto-Yglesias F.
      • et al.
      Systematic review of glucose control in non-critically ill hospitalized patients: a systematic review and meta-analysis.
      Professional organizations and governmental bodies have promulgated guidelines that, in general, recommend higher glucose targets than those of Van de Berghe et al to avoid hypoglycemia and also to mitigate the deleterious effects of hyperglycemia.
      American Diabetes Association
      Standards of medical care in diabetes – 2014.
      • Houlden R.
      • Capes S.
      • Clement M.
      • Miller D.
      Canadian Diabetes Association Clinical Practice Guidelines Expert Committee
      In-hospital management of diabetes.
      • Deedwania P.
      • Kosiborod M.
      • Barrett E.
      • et al.
      Hyperglycemia and acute coronary syndrome: a scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity and Metabolism.
      • Dellinger R.P.
      • Levy M.M.
      • Rhodes A.
      • et al.
      Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup
      Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.
      Achieving target range goals in critical care settings requires hourly or even more frequent glucose monitoring. The method for testing glucose levels is noted in some of the guidelines. The National Health Service of the United Kingdom recommends capillary finger-stick blood sampling in the perioperative period,

      Diabetes UK. The hospital management of hypoglycemia in adults with diabetes mellitus (Mar 2010). http://www.diabetes.org.uk/About_us/what-we-say/Improving-diabetes-healthcare/The-hospital-management-of-hypoglycaemia-in-adults-with-Diabetes-Mellitus/. Accessed July 28, 2014.

      the American Heart Association specifies that samples can be finger-stick–derived capillary blood,
      • Deedwania P.
      • Kosiborod M.
      • Barrett E.
      • et al.
      Hyperglycemia and acute coronary syndrome: a scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity and Metabolism.
      and the Canadian Diabetes Association states that bedside monitoring can be done if the hospital has an adequate proficiency testing program.
      • Houlden R.
      • Capes S.
      • Clement M.
      • Miller D.
      Canadian Diabetes Association Clinical Practice Guidelines Expert Committee
      In-hospital management of diabetes.
      However, the American Diabetes Association and the Society for Critical Care Medicine, while not proscribing POC BGMs, note that using them may be problematic because of (1) clinical conditions such as impaired perfusion due to hypotension and peripheral edema that interfere with accurate sampling of capillary blood and (2) technical limitations of the meters that affect accuracy, such as hypoxia in glucose oxidase–based meters, anemia, and certain medications such as acetaminophen.
      American Diabetes Association
      Standards of medical care in diabetes – 2014.
      • Dellinger R.P.
      • Levy M.M.
      • Rhodes A.
      • et al.
      Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup
      Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

      Regulatory Background

      The CMS regulates all laboratory testing (except research) on humans in the United States through regulations established by the Clinical and Laboratory Improvement Amendments (CLIA) of 1988.

      Centers for Disease Control and Prevention. Clinical Laboratory Improvement Amendments (CLIA). http://wwwn.cdc.gov/clia/Regulatory/default.aspx. Accessed July 28, 2014.

      The CLIA sets minimum quality regulations for laboratory testing regardless of whether a test is conducted in a formal, central laboratory or at the patient’s bedside for POC.

      Centers for Disease Control and Prevention. Clinical Laboratory Improvement Amendments (CLIA). http://wwwn.cdc.gov/clia/Regulatory/default.aspx. Accessed July 28, 2014.

      The BGMs currently in use for most hospitalized patients are categorized as “waived” under the CLIA. In the absence of accrediting agency or institutional requirements, facilities using CLIA-waived devices have minimal quality requirements. They need only pay a biennial certificate fee, follow the manufacturer’s instructions for use, and agree to unannounced inspections.
      The FDA issued a draft guidance for POC BGMs on January 7, 2014.

      Food and Drug Administration. Blood glucose monitoring test systems for prescription point-of-care use: draft guidance for industry and Food and Drug Administration staff. January 7, 2014. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM380325.pdf. Accessed July 28, 2014.

      This document presents future requirements for the clearance of POC BGMs for professional use, such as in hospitals. The FDA proposes to raise the classification of future cleared hospital-use glucose meters to the CLIA “moderate complexity.” Hospitals performing CLIA moderate complexity tests must currently (1) document operator training and annual competency, (2) verify method performance, (3) confirm the calibration and method correlation to central laboratory glucose every 6 months, (4) perform daily quality control, and (5) subscribe to a proficiency testing program. In addition, operators must have a high school diploma or higher education level documented in their employee records. Hospitals performing CLIA moderate complexity glucose testing must be inspected every 2 years during which the inspector must audit the educational documentation of a group of operators. Practically, changing the CLIA complexity of glucose meters will increase the regulatory burden for hospitals because most facilities have hundreds or thousands of operators performing testing.
      No POC BGM has ever been cleared by the FDA for critically ill patients.
      • Klonoff D.C.
      The Food and Drug Administration is now preparing to establish tighter performance requirements for blood glucose monitors.
      Therefore, these devices are being used “off-label” in the ICU, operating room, recovery room, and emergency department. The FDA has also recently instructed manufacturers to change their labeling of existing hospital glucose meters to include a statement that critically ill patients should not be tested with a BGM because results may be inaccurate. The off-label use of glucose meters is subject to CLIA “high complexity” regulations. The CLIA high complexity testing has even higher documentation standards than does CLIA moderate complexity testing and essentially prevents anyone without an associate degree in laboratory science or medical technology from performing testing. Many hospital staff members who currently perform POC blood glucose monitoring will be prohibited from this activity if the FDA labeling policies are enforced. The off-label use of a glucose meter will create 2 separate sets of requirements for hospitals to manage: one for “approved” use and the other for off-label use, which will challenge hospitals with managing 2 sets of different regulations.
      The CMS recently became aware that POC BGMs are being used in hospitals off-label and is ready to enforce the prohibition of their off-label use, according to 2 recent letters from the New York State Department of Health.

      New York State Department of Health. Re: Off-label use of glucose meters. January 13, 2014. http://www.pharmamedtechbi.com/∼/media/Supporting%20Documents/The%20Gray%20Sheet/40/19/NY%20State%20DOH%20Letter%20on%20Glucose%20Meters.pdf. Accessed July 28, 2014.

      New York State Department of Health. Off-label use of glucose meters. February 18, 2014. http://www.wadsworth.org/labcert/clep/files/FAQs_Off-label_Use_Glucose.pdf. Accessed July 28, 2014.

      Unlike drugs, cleared devices cannot be used off-label for a different clinical application. The off-label use of laboratory devices is forbidden by the CLIA unless the laboratory establishes its own performance specifications for use in that facility’s intended patient population to ensure accurate results. Yet, if a CLIA audit identifies off-label use of POC BGMs without appropriate evidence of compliance for CLIA high complexity testing, the hospital will be cited. A cited hospital is at risk of losing its CLIA certificate, that is, its license to perform testing, as well as having to pay fines for not complying with the CLIA high complexity requirements. After any citations are issued, it is possible that many US hospitals will eliminate POC BGM testing from critically ill settings. One of the unintended consequences may be the discontinuation of intensive insulin therapy, which requires frequent glucose measurements. Unfortunately, this announced enforcement would then adversely affect the management of diabetes in critically ill settings. A survey of hospitals about how they are planning to respond to this situation could provide predictive information, but it would be difficult to identify the decision maker in each hospital and get him/her to enumerate how he/she would or would not comply with the CMS.
      Currently, there is a standoff between hospital laboratories, industry, and the CMS. The FDA has invited POC BGM manufacturers to submit additional data demonstrating the accuracy of hospital-cleared POC BGMs for critically ill patients for these products to get a CLIA waiver and be used by any hospital staff person, but no company has publicly announced that it is ready to submit such data. Most hospitals have already conducted correlation data using typical patient samples from the hospital wards, but it is not clear which specific types of critically ill patients and how many of them must be tested.

      POC BGM Devices and Their Alternatives

      The alternatives to POC BGM testing are all slower, more difficult to work with, more expensive, and/or riskier for the patient than POC BGMs.
      • Madan A.
      • Kumar R.
      • Adams M.M.
      • Benitz W.E.
      • Geaghan S.M.
      • Widness J.A.
      Reduction in red blood cell transfusions using a bedside analyzer in extremely low birth weight infants.
      Centers for Disease Control and Prevention (CDC)
      Vital signs: central line-associated blood stream infections – United States, 2001, 2008, and 2009.
      Without POC BGMs, clinicians will be left measuring glucose using a central laboratory device (CLD), blood gas analyzer (BGA), or 1 of 3 nonstrip POC instruments (HemoCue [HemoCue America], iStat [Abbott Point of Care], or epoc [Epocal]; Table).
      TableCharacteristics of BGM Devices Currently Used in Critically Ill Settings
      Alt = alternate; Art = arterial; BGM = blood glucose monitor; Cap = capillary; CLD = central laboratory device; CLIA = Clinical and Laboratory Improvement Amendments; POC = point-of-care; Ven = venous.
      ParameterPOC BGMCLDBGAHemoCuei-Statepoc
      Analysis time5 s4 min60 s40-240 s130-200 s30 s
      Approximate TAT
      TAT is the total time required to complete the test and includes test ordering, blood draw, transport to the laboratory, analysis time, and result returning. Analysis time is device analysis time only.
      Up to 2 minCan be >1 h3-10 min3-6 min3-5 minUp to 3 min
      Sample typeCap, Ven, Art, Alt siteCap, Ven, ArtCap, Ven, Art, heel-stickCap, Ven, ArtVen onlyCap, Ven, Art
      Approximate sample volume (μL)0.3-1.220010056592
      Total cost ($)
      • Le H.T.
      • Harris N.S.
      • Estilong A.J.
      • Olson A.
      • Rice M.J.
      Blood glucose measurement in the intensive care unit: what is the best method?.
      0.75
      Approximate published cost for disposable only. All other costs not included.
      2.010.881.50
      Approximate published cost for disposable only. All other costs not included.
      5.00
      Approximate published cost for disposable only. All other costs not included.
      16.00
      Approximate published cost for disposable only. All other costs not included.
      CLIA complexityNot clearedModerateModerateWaivedWaivedModerate
      Available at POCYesNoNoYesYesYes
      a Alt = alternate; Art = arterial; BGM = blood glucose monitor; Cap = capillary; CLD = central laboratory device; CLIA = Clinical and Laboratory Improvement Amendments; POC = point-of-care; Ven = venous.
      b TAT is the total time required to complete the test and includes test ordering, blood draw, transport to the laboratory, analysis time, and result returning. Analysis time is device analysis time only.
      c Approximate published cost for disposable only. All other costs not included.

      CLDs and BGAs

      Central laboratory devices require a whole blood specimen (usually >1 mL) to be spun for analysis. They are subject to many types of preanalytical errors, including incorrect sampling.
      • Sacks D.B.
      • Arnold M.
      • Bakris G.L.
      • et al.
      Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus.
      The turnaround time (TAT) can be well over 1 hour.
      • Kilgore M.L.
      • Steindel S.J.
      • Smith J.A.
      Evaluating stat testing options in an academic health center: therapeutic turnaround time and staff satisfaction.
      The intense labor required for CLD testing includes blood drawing, specimen transport, laboratory processing, sample analysis, and result reporting. Under ideal circumstances, the fastest time possible is usually approximately 25 minutes.
      • Le H.T.
      • Harris N.S.
      • Estilong A.J.
      • Olson A.
      • Rice M.J.
      Blood glucose measurement in the intensive care unit: what is the best method?.
      Blood gas analyzers are much like CLDs, with a similar accuracy profile. The TAT is dependent on location. Blood gas analyzers are usually placed in selected strategic locations (eg, the operating room or the ICU), require frequent maintenance, and are expensive when measuring only glucose. Central laboratory devices and BGAs are both CLIA moderate complexity tests, demanding highly trained personnel, with laboratory technologists running the CLDs and oftentimes registered nurses running the BGAs.

      POC Nonstrip Devices (HemoCue, iStat, and epoc)

      Three POC devices, using inserted cartridges, are available in the United States: HemoCue, i-Stat, and epoc. There are few accuracy studies for these devices
      • Torjman M.C.
      • Jahn L.
      • Joseph J.I.
      • Crothall K.
      Accuracy of the hemocue portable glucose analyzer in a large nonhomogeneous population.
      • Leino A.
      • Kurvinen K.
      Interchangeability of blood gas, electrolyte and metabolite results measured with point-of-care, blood gas, and core laboratory analyzers.
      • Gijzen K.
      • Moolenaar D.L.
      • Weusten J.J.
      • Pluim H.J.
      • Demir A.Y.
      Is there a suitable point-of-care glucose meter for tight glycemic control? Evaluation of one home-use and four hospital-use meters in an intensive care unit.
      • Kos S.
      • van Meerkerk A.
      • van der Linden J.
      • Stiphout T.
      • Wulkan R.
      Validation of a new generation POCT glucose device with emphasis on aspects important for glycemic control in the hospital care.
      • Stotler B.A.
      • Kratz A.
      Analytical and clinical performance of the epoc blood analysis system: experience at a large tertiary academic medical center.
      and little data in the critical hypoglycemic range (<70 mg/dL) reported for any of them. The TAT is limited to specimen drawing and device analysis, which is substantial for HemoCue and i-Stat and less for the epoc system compared with that for modern POC BGM devices. The analysis time difference of a few minutes can be a drawback for a busy nurse. The cost of these 3 POC systems is much higher than the cost of POC BGM testing. In our experience, from a human factors standpoint, these 3 devices are more difficult to use than POC BGM devices, which is not surprising considering the many years of design glucose monitoring devices have undergone for easy use by lay people. Because the data suggest that they are no more accurate than the newer strip-based meters, there would have to be substantial improvements in human factors and costs to justify the limitation of testing to these POC devices in critically ill patients.

      Recommendations

      A 5-year moratorium by the CMS is needed to delay (1) enforcement of the FDA requirement for manufacturers to change their labeling indicating “test not validated in critically ill populations” and (2) elevation of glucose meters to CLIA moderate complexity devices. This moratorium will allow the diabetes community to prepare for converting to new testing methods if adequate performance data cannot be collected. For the moratorium period to be effective, all the stakeholders in POC blood glucose monitoring must find ways to make current technology work, or else they must find replacements for current technology. Clinicians can use this moratorium period (1) to identify the types of acutely ill patients on whom to use or not use POC BGMs, (2) to develop a consensus definition of “critically ill” because it is these patients who are going to be affected by the CMS’ announced impending enforcement of the off-label, high complexity status of BGMs, (3) to conduct modeling and empiric studies about which outcomes are associated with using POC BGMs of various levels of accuracy compared with using alternative methods, and (4) to develop new workflow processes if POC BGMs may no longer be available in these populations. The FDA can use this period to work with industry to encourage the submission of performance data in cleared-hospital BGMs from selected types of critically ill patients so that these products can be CLIA-waived for at least some of these patients. Industry can use this period to develop next-generation products that will be more accurate than the current ones and more likely to become CLIA-waived. Innovation will be needed in light of the 2014 draft guidance for POC BGMs presenting the strictest levels of accuracy ever proposed by the FDA for any type of BGMs.

      Conclusion

      The POC BGMs were never cleared for critically ill patients, but they have become the standard of care. The CMS regulators are now studying whether to cite hospitals for using this tool in critically ill patients unless their performance is validated extensively in this population, and such validation does not appear to be forthcoming in the near future. This tool might be removed from critically ill patients with no good alternatives. Because of the high cost, poorly studied accuracy, and long analysis time required for the current POC alternatives, this suddenly contemplated regulatory policy toward POC BGMs would have highly negative unintended consequences. Immediate enforcement of such a policy at this time would set back hospital diabetes care by decades. A moratorium would allow time for clinicians and industry to adjust to the necessary stricter standards that will govern POC BGMs and affect the practice of medicine for these types of patients in the future.

      Acknowledgments

      Katrina S. Thollaug and Rebecca Corey Astrom provided editorial assistance.

      Supplemental Online Material

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