STATUS OF CAPILLARY GLUCOSE ESTIMATION IN POINT-OF-CARE TESTING

STATUS OF CAPILLARY GLUCOSE ESTIMATION IN POINT-OF-CARE TESTING

PRINCIPLE:

Point of Care Testing (POCT) refers to those analytical patient testing activities provided within the hospital, but performed outside the laboratory. Activities of the POCT program must comply with all current standards for laboratory accreditation, regardless of the scope of testing. Designated laboratory personnel have centralized the coordination of the POCT program. Glucose meters are widely used in many areas including hospital wards and clinics, general practice, operating theatres, ambulances, pharmacies, aboriginal health care centres and by patients at home for self-monitoring. Such testing involves the use of a glucose measuring meter, a specific blood glucose test strip and appropriate quality control material. This will be referred to here under as the Glucose system. Glucometers are classified into Class II devices according to US FDA which means they should fulfill following criteria

•Require 510(k) clearance prior to marketing

•Substantial equivalence to predicate

•FDA evaluates intended use, performance, labeling

FDA clears glucose meters for the following indications:

─Quantitative measurement of glucose in whole blood (e.g., capillary, venous, arterial)

─Intended for self testing outside the body (in vitro diagnostic use) by people with diabetes

─ As an aid in monitoring the effectiveness of diabetes control program

─ NOT intended for the diagnosis of or screening for diabetes

-     Testing sites - fingertip and alternative sites (e.g. forearm, palm, calf, thigh)

– A few are cleared for use on neonates

Majority of meters are designed and validated for OTC use

v  The majority of meters used in hospitals are OTC devices

v  CLIA waived by regulation – used anywhere in the professional healthcare setting

v  ISO 15197 accuracy criteria for OTC use

v  User is not the intended user

Following are taken into account when using these devices:

 The limitations of the system when used in specific settings such as critical care units, obstetric wards and neonatal units

 The effects of physiological and pathological interferences such as haematocrit, various drugs and various intravenously administered solutions

 Other potential interfering substances

The analytical performance (precision and bias) of glucose systems should be designed to match the clinical application of the test. This document outlines recommendations aimed at improving the use of glucose systems for patient care.

Recommendations from Australian Association of Clinical Biochemist

1. All glucose systems used by health professionals for patient management should participate in an EQA program. Review and communication of the performance of each meter in such programs should become a routine practice for each site.

2. It is highly desirable to run a quality control sample daily. This ensures ongoing validation of the test strips.

3. It is recommended that glucose systems which have features designed for professional use are implemented in acute hospital facilities, not systems designed for home use. This will allow results to be downloaded to patient information systems so results are part of the patient record. This ensures more effective use of results in patient management. Improved patient management for diabetes will justify increased capital outlay for professional glucose meters.

4. Glucose systems used in hospital facilities should allow patient identification as well as the capacity to be connected to other systems and/or networks.

5. The health care professional managing the patient should decide on the glucose system most suitable to the patient setting, taking into account the relevant professional scientific advice available for each device.

6. Glucose estimations performed in Intensive Care Units should be performed on a blood gas machine or device of similar analytical performance.

7. It is highly desirable that the tolerance for analytical bias (accuracy) and imprecision of glucose systems in other hospital areas should be less than 10% variance from the true value.

8. Glucose systems accuracy should be confirmed by an accredited laboratory method at least once every 12 months. If analytical performance is less than that required, the glucose system should be replaced.

9. A standardised training package for health professionals and patients is essential. As a minimum health care professionals should complete an online competency program such as that provided by The Australian Point of Care

Practitioner’s Network (APPN) which is currently funded by the Australian Government through the Quality Use of Pathology Program (www.appn.net.au).

10. It is recommended that all incidents and adverse events are reported to TGA through the IRIS system (http://www.tga.gov.au/safety/problem-device.htm)

11. The performance of capillary blood glucose system should be validated by an appropriately accredited clinical laboratory. Such validation should follow the protocol published by the AACB PoCT Committee. This validation report must be a minimum requirement prior to the introduction of a ward based glucose testing system in a hospital.

12. Glucose meters designed for self-monitoring at home should not be used to monitor tight glycaemic control.

13. It is desirable to assess performance glucose systems designed for self-monitoring in the hands of patients as well as health care professionals.

Confirmation Testing:

Critical (panic) values obtained on glucometer are required to be followed up with confirmation laboratory testing. This is accomplished by nursing personnel either: a. drawing a specimen and keying in a POC Confirmation Glucose or

b. if regular lab is being or has been drawn immediately prior to test, the nursing personnel will notify the lab of the critical POC value to expedite confirmation testing of the glucose. If the lab office is notified, they must pass the information to Routine Chemistry, Trauma Lab, or Outpatient Lab, whichever will be performing the test.

All confirmation testing is to be handled as high priority. Confirmatory test results are called to the appropriate nurse or physician in charge of the patient. This will provide verification of POC values or initiate exchange of the Inform monitor by nursing personnel to ensure quality patient care.

A number of different studies have examined the accuracy of bedside glucose meters in various patient populations with either hypotension, poor peripheral perfusion, or edema. Two studies done on patients in the emergency department and ICU with hypotension (systolic blood pressure less than 80 mm Hg) both found that capillary glucose measurement systematically underestimated venous glucose in this patient population. (1,2) In contrast, another study performed on 75 patients with systemic hypoperfusion (defined as systolic blood pressure less than 90 mm Hg or requirement for vasoactive agents) found relatively good agreement between capillary whole blood and arterial whole blood glucose, with 95% limits of agreement of approximately [+ or -]30 mg/dL. (3) Finally, a recent study comparing capillary whole blood to venous plasma glucose in patients with poor peripheral perfusion related to vasopressor use or peripheral edema found that in both categories of patients (poor perfusion and peripheral edema), capillary whole blood glucose systematically overestimated venous plasma glucose. Even in this study, however, almost all results agreed within approximately 2 mmol/L (36 mg/dL) glucose. (4)

In recent years, numerous studies have been published analyzing the accuracy of glucometers specifically in the setting of neonatal hypoglycemia. Ho, et al. (5) reported on the sensitivity and negative predictive value of 5 glucometers in detecting neonatal hypoglycemia. They found that not even 1 of the 5 was able to meet the ADA standards, whereas 2 of the devices were able to meet the NCCLS standards. Khan, et al. (6) compared 7 glucometers and reported agreement between glucometer readings in the hypoglycemic range but found wide discrepancy in the correlation between reference and POCT devices both in the hypo and hyperglycemic range to the tune of 60%. The study by Ngerncham, et al. (7) appearing in this volume of the journal too has used an elegant split sample design and meticulously compared OneTouch SureStep Hospital Test Strips (photometric glucose oxidase system) with a Nova StatStrip (modified glucose oxidase based amperometric system) using Roche Modular P 800 for the reference laboratory measurement. Another recent study reported good correlation as well as recommended their use in neonatal clinical practice (8). All these studies highlight that POC devices may be used as screening devices for neonatal hypoglycemia, but confirmation of hypoglycemia with laboratory measurement of plasma glucose is still crucial.

It needs to be realized that laboratory estimation too is fraught with preanalytical (sample collection, transport and physiological factors) errors. POCT devices are prone for both pre-analytical and analytical errors (precision of the device being used). The comparison of POCT devices with laboratory sample which has been poorly processed can lead to erroneous estimation of discrepancy where little or none may exist. Any further studies on comparison of POCT devices with reference standard should focus on comparing improved second generation POCT devices with a reference laboratory device taking utmost care to ensure precise laboratory estimation without any processing delays and fall in glucose secondary to glycolysis.

Australian Diabetes Educators Association

The Australian Diabetes Educators Association (ADEA) promotes the reliable and accurate use of blood glucose meters within the health care setting and in diabetes self management.

ADEA recommends:

 Blood glucose meters not be used as a method of screening for diabetes.

 Testing at the point of care may be appropriate in defined circumstances, such as in remote indigenous communities where laboratory testing is unavailable and postponement of treatment would be potentially harmful for the individual. The meter used at the point of care must have a vigorous quality improvement program in use.

 Outside of the acute clinical setting, blood glucose meters only be used to monitor blood glucose levels in people with a confirmed diagnosis of diabetes.

 Appropriateness of self blood glucose monitoring be assessed on an individual basis, taking into consideration the person’s disease and co-morbidity status, age, culture, dexterity and physical and intellectual capabilities, identified glycaemic targets, current medication regimen, potential confounders that may interfere with the accuracy of results obtained, and level of motivation.

 All people with diabetes using insulin therapy are encouraged to perform blood glucose monitoring.

 Individuals using blood glucose meters have access to a health professional deemed competent in the use of the meter.

 Further diabetes education is essential to ensure self management behaviours are underpinned by a sound knowledge of how dietary intake, physical activity, medication, stress and illness all interact to affect blood glucose levels.

 Although some blood glucose meters allow the measurement of glucose levels from small samples of blood from the forearm and other sites, blood taken from the capillary bed of the fingertip is the preferred sample, particularly when blood glucose levels are changing rapidly.

 Health professionals only use blood glucose meters after successfully completing an education program that results in the attainment of competency in meter operation, control testing and problem solving.

 Quality improvement practices are implemented within clinical settings to ensure both blood glucose monitoring equipment and operators meet high standards of performance and process.

 All health services using blood glucose meters provide:

Ø  a well-defined policy and procedure

Ø  a training program for personnel performing the tests

Ø  quality improvement procedures

Ø  regular equipment maintenance

Ø  external auditing of meters

Ø  appropriate lancet devices that meet infection control considerations.

 In certain clinical situations different strip technology may be more appropriate than others, such as in the care of patients using icodextrin dialysate solution, or patients receiving intravenous preparations containing maltose. In these situations it is essential to consult product information and/or the manufacturer of the glucose meter and test strip to ensure icodextrin and maltose do not interfere with blood glucose readings.

 Blood glucose measurement using portable blood glucose meters not be used in isolation when evaluating the glycaemic control of people with diabetes.

Substances or Conditions That May Contribute to Total Analytical Error in Consumer and Hospital Glucose Meters Interferant Reference

ü  Hematocrit

ü  Ascorbate

ü  Maltose

ü  Galactose or Xylose

ü  Acetaminophen

ü  Partial Pressure of Oxygen

ü  Dopamine

ü  Mannitol

ü  Altitude or hypoxia

Numerous studies have been published reporting the performance of blood glucose monitoring systems. The results of these studies are often conflicting. Correct evaluation is, however, complex, and the apparent contradiction of results creates confusion. One recent article (9) provides an overview of frequently made errors in the evaluation of devices and develops an easy-to-use checklist to verify the quality of such studies. This checklist was used with 20 representative studies selected from the literature between 2007 and 2012. The process revealed that limitations on the designs and methods of studies assessing the performance of blood glucose systems are common.
The use of the accuracy checklist showed that 40% of the studies showed clear nonconcordance with ISO 15197. The use of the interference checklist showed that only half of publications were in good agreement with the quality checks. The author concluded that many evaluations are performed poorly, and often present questionable conclusions due to the fact that few publications adhere to international guidelines. Others have also assessed the quality of glucose monitor studies and came to similar conclusions.
In the article by Mahoney and Ellison,(10)52 reports were reviewed, none of which conformed to all 38 STARD and CLSI recommendations. Future studies evaluating glucose monitoring systems should be carefully designed and should follow published recommendations to assess the quality of glucose measuring devices

References:
1. Atkin SH, Dasmahapatra A, Jaker MA, Chorost MI, Reddy S. Fingerstick glucose determination in shock. Ann Intern Med. 1991;114:1020-1024.
2. Sylvain HF, et al. Accuracy of fingerstick glucose values in shock patients. Am J Crit Care Med 1995;4:44-48.
3. Kulkarni A, et al. Analysis of blood glucose measurements using capillary and arterial blood samples in intensive care patients. Intensive Care Med. 2005;31:142-145.
4. Kanji S, et al. Reliability of point-of-care testing for glucose measurement in critically ill adults. Am J Crit Care Med. 2005;33:2778-2785.

5. Ho HT, Yeung WK, Young BW. Evaluation of point of care devices in the measurement of low blood glucose in neonatal practice. Arch Dis Child Fetal Neonatal Ed. 2004;89:F356-9.

6. Khan AI, Vasquez, Y, Gray J, Wians FH, Kroll MH. The variability of results between point of care testing glucose meters and the central laboratory analyzer. Arch Pathol Lab Med. 2006; 130: 1527-32.

7. Ngerncham S, Piriyanimit S, Wongsiridej P, Inchgarm L, Kitsommart R, Vutrapongwatana P, et al. Validity of two point of care glucometers in the diagnosis of neonatal hypoglycemia. Indian Pediatr. 2012;49: 621-5.

8. Makaya T, Memmott A, Bustani P. Point-of-care glucose monitoring on the neonatal unit. J Pediatr Child Health. 2012;48:342-6.

9. Thorpe GH. Assessing the quality of publications evaluating the accuracy of blood glucose monitoring systems. Diabetes Technol Ther. 2013;15(3):253-259.

10. Mahoney J, Ellison J. Assessing the quality of glucose monitor studies: a critical evaluation of published reports. Clin Chem. 2007;53(6):1122-1128.