The inaccuracy of venous and capillary blood glucose measurement using reagent strips in the newborn period and the effect of haematocrit

The purpose of this study was to compare the accuracy of capillary and venous reagent strip tests (RST) against a reference plasma glucose method, and to assess the impact of haematocrit. One hundred and eighty infants admitted to the Neonatal Unit had blood glucose measured by reagent strip tests using capillary and venous blood samples. Venous plasma glucose was assayed by the Hexokinase method. Each infant had a venous haematocrit performed in the Neonatal Unit. Comparable inaccuracies were noted with both capillary and venous reagent strip tests at all levels. The mean difference between capillary RST and plasma glucose was 0.058 mmol/l (S.D. 1.39). The corresponding mean venous RST plasma glucose difference was 0.138 mmol/l (S.D. 0.96). The two means were statistically different from each other (P = 0.024), but this difference disappeared if the comparison was made only in babies with a PCV of 35-55%. At higher haematocrits (PCV >55%, N= 96) the mean difference between venous RST and plasma glucose was significantly more than the mean difference between capillary RST and plasma glucose (0.018 versus 0.295. P = 0.002). Hence the higher the haematocrit the more inaccurate the venous RST. This study confirms the limited value of reagent strip tests in the assessment of blood glucose in the neonatal period. It suggests that venous RST may be more inaccurate in comparison to capillary and that high haematocrits have a greater effect on venous RST than capillary RST.     

Determining the best method for first-line assessment of neonatal blood glucose levels

OBJECTIVE: To evaluate and compare the accuracy and performance of two electrochemical glucose meters. To determine the user acceptability of these glucose meters and the ABL 620 Blood Gas Analyser (Radiometer, Copenhagen, Denmark) with an electrochemical glucose oxidase electrode for use in a Level 2 special care baby unit. METHODOLOGY: A total of 108 blood samples were collected from 47 babies at risk for hypoglycaemia. The blood glucose level was measured with two glucose meters, the Advantage Glucose Meter (Roche Diagnostics, Castle Hill, Australia) and the Precision-G Blood Glucose Testing System (Medisense, Melbourne, Australia), and the true blood glucose (TBG) measured with the ABL 620 blood gas analyser. Results from the glucose meters were compared with the TBG (as a percentage of the TBG). RESULTS: The mean (SD) percentage difference between the Advantage Glucose Meter and TBG was 4.5% (12. 5), and Precision-G Glucose Meter and TBG was 15.4% (12.4). The sample haematocrit did not significantly influence the glucose meter/TBG differences. There was an overall preference by the nursing staff for the Advantage Glucose Meter. CONCLUSIONS: The Advantage Glucose Meter was significantly more accurate than the Precision-G with similar precision. It was the preferred method of screening for neonatal hypoglycaemia.     

Comparison of two strip test methods of whole blood glucose measurement in the neonatal period

The aim of this study was to compare the performance and accuracy of the BM Strip test used in conjunction with Reflectance photometry, and the new non-wipe strip test (Advantage) against a reference plasma glucose method. In total, 114 newborns consecutively admitted to the Neonatal Unit over a 6 mo period were enrolled into the study. Each newborn had their venous blood glucose measured by the BM Strip test and Advantage glucometer and the venous haematocrit was also determined. Plasma glucose was measured in the laboratory by the hexokinase method. The mean difference between the BM Strip test and plasma glucose was significantly less than the corresponding value for the Advantage glucometer (0.312, 95% confidence interval (CI) 0.11-0.51 vs 0.766, 95% CI 0.57-0.95], although the limits of agreement between both methods and plasma glucose were wide. Haematocrit did not influence significantly the accuracy of either test.     

Comparison of two methods of measurement of whole blood glucose in the neonatal period

The purpose of this study was to compare the performance and accuracy of the HemoCue B-Glucose photometer system and reagent strip tests used in conjunction with reflectance photometry against a reference plasma glucose method. One hundred consecutive babies admitted to the neonatal unit over a 6-month period were enrolled in the study. Each baby had a heelprick capillary glucose measured by HemoCue and reagent strip tests. At the same time venous plasma glucose and haematocrit were measured. The mean difference between the reagent strip test and plasma glucose was significantly less than the corresponding value for the HemoCue (0. 015 ± 1. 41 vs 0. 837 ± 1. 565 mmol 1^-1, mean ± SD); however, the agreement limits between both methods and plasma glucose were wide. No significant effect of haematocrit was detected on either method. The HemoCue photometer does not offer any advantage over the widely used reagent strip tests in the neonatal period. However, the limits of agreement of both methods compared with plasma glucose are too wide to be clinically acceptable in the neonatal period.     

Capillary (heelstick) versus venous blood sampling for the determination of glucose concentration in the neonate.

Various sites may be used to obtain blood (plasma) for the determination of the glucose concentration in the neonate. Because multiple sites may be sampled in the same neonate, it is important to determine the variability in blood glucose concentration which may result from such sampling. Since pain and mechanical forces may be different because of the method used to obtain the capillary (heelstick) blood compared to the venous specimen, the two sites were sampled, and the blood glucose concentration was determined simultaneously in 25 asymptomatic well neonates whose mean birth weight was 2,562 +/- 152 g and whose gestational age was 35.5 +/- 1.5 weeks. There was a significant (p less than 0.0001), but relatively weak correlation (r2 = 0.64) between capillary (heelstick) blood and venous blood relative to blood glucose concentration. When the capillary (heelstick)-venous glucose concentration difference was compared to the mean of the capillary (heelstick) and venous glucose concentrations, a difference of +/- 0.5 mM (9 mg/dl) was noted in 3 of 25 neonates. Appropriately obtained capillary (heelstick) blood samples provide measurement of blood glucose concentration which are variable compared to venous samples, but which are probably not significant physiologically.     

Measuring blood glucose in neonatal units: how does hemocue compare?

Rapid and reliable determination of blood glucose concentration is essential during the neonatal period to prevent adverse neurodevelopmental outcome from hypoglycaemia. Despite their unreliability, reagent strip methods continue to be used extensively in neonatal nurseries due to their rapidity and convenience. Recently, a new portable laboratory standard technique has been introduced (HemoCue B-Glucose system) for whole blood glucose determination. It is particularly suitable for near-patient testing in neonatal units. This new method, as well as other established methods of whole blood (Yellow Springs Instrument (YSI) and a hexokinase method on Cobas Bio), and plasma (Kodak Ektachem) glucose measurement, were therefore evaluated for their accuracy and concordance of measurements taken in the neonatal period. There were substantial discrepancies among the four methods of glucose measurement with wide limits of agreement between these methods. The glucose concentrations measured by HemoCue and YSI (n = 206), HemoCue and hexokinase (n = 113), HemoCue and plasma glucose on Ektachem (n = 69) and hexokinase and Ektachem (n = 66) were likely to differ by -29 to +61%, -23 to +56%, -36 to +65%, and -19 to +30%, respectively. Even the laboratory methods of blood glucose determination, therefore, can not be used interchangeably. Using a model based approach, the probabilities of "discordant" classification as hypo- or normo-glycaemia were estimated to be 6.8%, 6.5%, and 7.1% between HemoCue and YSI, HemoCue and hexokinase on Cobas Bio, and HemoCue and Ektachem analysers, respectively. In view of these low probabilities of discordant classification with other glucose analysers, the HemoCue system may offer a reasonable compromise between bedside and laboratory blood glucose estimations in neonates.     

Validation of capillary glycemia as a strategy for the screening of diabetes mellitus in adolescents

Objective: To compare the degree of concordance between plasma and capillary glucose for screening of diabetes mellitus in adolescents.
Methods: The plasma and capillary glucose of 119 adolescents aged 10–19 yr (36 males and 83 females) from public schools in Niterói, Rio de Janeiro State, Brazil, were verified after a 12-h fast. Agreement was assessed through kappa statistics (k), McNemar's chi-squared test, and the intraclass correlation coefficient (ICC). The paired Student's t -test for comparison of means, the approaches by Altman and Bland, and the survival–agreement plot were also applied.
Results: Mean values of plasma glucose were 7.9 points higher than the capillary values (91.5 vs. 83.6 mg/dL, p < 0.001; ICC = 0.419). A regular agreement between the methods (k = 0.31, p < 0.001) for assessing proportions of adolescents with glycemia ≥100 mg/dL is observed. Using the strategy of adding 8 mg/dL to the capillary levels, the agreement improved (k = 0.46, p < 0.001) and a significant difference was not observed between the estimated prevalences (p = 0.815).
Conclusions: The results suggest a satisfactory agreement between the two methods when capillary glucose is corrected, and this may be a useful and low-cost tool for the epidemiologic investigation of diabetes mellitus prevalence in adolescents.     

Subcutaneous infusion and capillary "finger stick" sampling of stable isotope tracer in metabolic studies

Metabolic studies utilizing stable isotope tracer in humans have typically used intravenous tracer infusions and venous blood sampling. These studies explore subcutaneous infusion of isotope and "finger stick" capillary blood sampling to measure glucose turnover. Five subjects received simultaneous 8-h infusions of glucose labeled with isotope: [1-(13)C]glucose subcutaneously and [6,6-(2)H(2)]glucose intravenously. At regular intervals, venous and finger stick blood specimens were obtained. Finger stick blood was applied to filter paper. Substrate and isotopic steady state was reached after 7.0 h with both routes of infusion. The isotopic enrichments of finger stick and venous specimens did not differ significantly for the subcutaneously infused [1-(13)C]glucose (p = 0.33 and p = 0.23, respectively) but the finger stick [6,6-(2)H(2)]glucose enrichment was slightly higher (p < 0.03) than that of the venous sample. Using [6,6-(2)H(2)]glucose infusion and venous plasma sampling as the reference method, the [1-(13)C]glucose gave estimates of glucose R(a) that were 13% (plasma) and 17% (finger stick) lower (p < 0.001 and p < 0.02, respectively). This difference could be attributed to recycling of (13)C label. In conclusion, subcutaneous infusion and finger stick specimen collection onto filter paper represent a potential method of conducting in vivo studies of substrate metabolism outside of a hospital-based research unit.     

Use of buffy-coat smears in the diagnosis of septicaemia in children

Gram-stained buffy-coat smears from venous and capillary blood samples in 105 children suspected of septicaemia were examined for the presence of bacteria and the results compared with blood culture isolates. Gram-positive and Gram-negative bacteria were identified in 18 venous (44%) and 19 capillary (46%) buffy-coat preparations in 41 instances where bacterial organisms were isolated from the blood cultures. It is concluded that the examination of buffy-coat smears for bacteria in children suspected of septicaemia is a useful adjunct to blood cultures and, in areas where no facilities exist for culture of blood, may be a simple and rapid method of establishing the diagnosis of bacteraemia in suspected patients.     

Determination of C-reactive protein (CRP) in capillary blood--a comparison with the CPR level in venous serum

C-reactive protein (CRP) has served as a reliable indicator of infectious and inflammatory diseases for a long time. Sequential CRP determinations offer a useful means of monitoring clinical courses and therapeutic effects in patients of any age as its serum concentrations correlate well with clinical symptoms. Especially in pediatric patients, however, venous blood sampling causes many problems. Thus, in our study a new method of CRP analysis from capillary plasma samples was tested and compared with CRP determinations from venous serum samples. 101 pairs of samples simultaneously obtained from 64 pediatric and neonatal patients (mean age of 5.8 months: min. 1 day, max. 5.5 years) were analyzed and compared. A good correlation (r = 0.967) was found for the whole range of measured CRP-concentrations (5-175 mg/l), showing a linear relationship between both methods. Results were analyzed by chi 2-test. Using a cutoff level of 5 mg/l, a sensitivity of 96%, a specificity and a positive predictive value of 98% each and an efficiency of 97% was found. Thus, the CRP determination from capillary blood samples offers a reliable method and a useful alternative for conventional analysis from venous serum.     

Comparison of antithrombin III, protein C and protein S levels in capillary and venous blood of newborn infants

The plasma concentrations of antithrombin III, protein C and protein S in capillary and venous blood samples obtained simultaneously from 30 neonates were compared in order to determine the suitability of using capillary blood for estimation of these proteins with anticoagulant action. Our findings showed that while capillary and venous blood did not differ significantly in antithrombin III functional activity and protein C antigen levels, the capillary samples had significantly lower protein C functional activity and higher antithrombin III antigen level. Protein S antigen level was also significantly higher in the capillary samples although the difference was relatively small. The capillary and venous concentrations of the binding protein of protein S, C4b binding protein, were almost identical.     

A clinical audit of cotside blood glucose measurement in the detection of neonatal hypoglycaemia

An evaluation of the use of cotside blood glucose measurement by BM Reflolux was undertaken as part of a unit audit programme. During the study period, 383 paired samples were obtained for both cotside and laboratory analysis. There were 328 results from the cotside which were less than 4 mmol/L. Cotside measurements consistently underestimated laboratory measurements but the differences were not related to age, gestation, weight or haematocrit. The difference between cotside measurements and laboratory results was greater at lower blood glucose values. Confidence and prediction intervals of blood glucose values from cotside measurement suggest that this technique is not reliable for the diagnosis of hypoglycaemia in the newborn. Indiscriminate and uncontrolled use of cotside glucose monitoring should not be relied upon for clinical management.     

Blood glucose monitoring by children at home: A comparison of methods

Abstract The accuracy of measurements of blood glucose performed at home by the index children and/or parents was compared using the Boehringer Mannheim reagent strips, Ames Visidex-2 strips, an Ames Glucometer and a Boehringer Mannheim Reflolux reflectance meter.
Capillary plasma samples, collected simultaneously, were later analysed by a Beckman glucose oxidase analyser. The coefficent of correlation between the self-monitored results (SMR) and the laboratory-analysed results (LAR) ranged from 0.59 to 0.92, the composite being 0.74. The mean difference between the SMR and the LAR was 1.0 mmol/l.
The occurrence of potential errors of management due to incorrect SMR results was determined. On four occasions, the SMR was greater than 6 mmol/l when the LAR was less than 3 mmol/l, and on 36 occasions a discrepancy greater than 50% occurred between the two values, without resulting hypoglycaemia.     

Umbilical cord blood lactate in normal infants: comparison between two methods of measurement

OBJECTIVES: Firstly, to determine the accuracy of the Radiometer ABL 625 lactate electrode (Radiometer Medical Pty Ltd, Nunawading, Victoria, Australia) by comparing the lactate values obtained by this method to those obtained with the Hitachi 917 lactate analyser (Boehringer Mannheim Corporation, Charlottetown, Prince Edward Island, Canada). Secondly, to determine the effect of delay in measurement on blood lactate levels. METHODOLOGY: Umbilical venous (UCV) blood samples were obtained from healthy term infants delivered vaginally. Lactate levels were measured with the Radiometer ABL 625 lactate electrode in the Neonatal Intensive Care Unit, Westmead Hospital and with the Hitachi 917 lactate analyser in 49 paired samples. In addition 26 UCV blood samples were placed in ice slurry and a further 26 samples at room temperature and blood lactate was measured at 5-min intervals for 30 min to determine the change of lactate levels with time. RESULTS: The lactate levels obtained from the Radiometer ABL 625 lactate electrode were consistently lower than the levels obtained from the Hitachi 917 lactate analyser (mean difference - 0.24), but the correlation was high (r = 0.97). The blood lactate levels increased at the rate of 0.012 mmol/L per min if the blood was left at room temperature. The lactate levels remained stable for 20 min if the blood was placed in ice slurry. CONCLUSION: The Radiometer ABL 625 lactate electrode was easy to use and there was high correlation with the values obtained by the standard laboratory method. The blood specimen must be place in an ice slurry if a delay in analysis is anticipated.     

Cotside plasma rather than whole blood estimates of blood glucose in the newborn

Abstract An evaluation of the use of a glucose reflectance meter for the cotside measurement of plasma rather than whole blood glucose was undertaken. Three hundred and twelve samples were obtained for examination. There is a closer correlation between plasma glucose than whole blood glucose to laboratory values. Confidence and prediction intervals show that even separating plasma from whole blood at the cotside does not improve the reliability of glucose reflectance meters when predicting blood glucose values in the context of managing high risk newborn infants. The cotside measurement of blood glucose using glucose reflectance meters should be abandoned and improved methods for quickly obtaining accurate laboratory data should be instituted.     

Evaluation of the Glucometer Elite XL device for screening for neonatal hypoglycaemia

To prevent persistent neurodevelopment and physical growth deficits in neonatal care, it is mandatory to determine blood glucose levels as quickly and precisely as possible, preferably using micro-methods. However, most commercially available instruments have not been validated and approved for this purpose. The aim of this study was to validate the Glucometer Elite XL, a newly developed device for point-of-care testing (POCT). In samples from 869 newborn infants, glucose levels were simultaneously measured by the Glucometer Elite XL in whole blood and by an accepted clinical laboratory method in haemolysed blood using the ECA 2000 device. An acceptable method agreement was found between the POCT and the ECA 2000 method (mean difference 0.013 mmol/l, SD 0.69). As determined by regression analysis (Passing-Bablok), the slope was 1.086 with a y-intercept of –0.4 mmol/l ( r =0.959, P <0.05). The differences between measurement pairs of both assays versus the haematocrit were negligible. With a cut-off for hypoglycaemia at 2.6 mmol/l glucose in haemolysed blood, the sensitivity of the POCT device was 0.63 and specificity was 0.98. Raising the cut-off of the Glucometer Elite XL to 3.2 mmol/l, the sensitivity and specificity incremented to 1.0 and 0.89, respectively. Conclusion:The Glucometer Elite XL instrument can be recommended for point-of-care blood glucose measurement in newborn infants if its character as a screening method is taken into account. To compensate deviating results, we advise to shift its cut-off for hypoglycaemia recognition to a safe threshold of 3.2 mmol/l. However, hypoglycaemia has to be confirmed by a valid glucose measurement in the clinical laboratory.     

Forearm blood glucose testing in diabetes mellitus.

AIMS: To compare the accuracy and acceptability of capillary blood glucose testing from the forearm with finger prick testing in diabetic children. METHODS: Blood glucose measurements from samples taken from the forearm and the finger were compared in an outpatient setting from 52 children and adolescents with diabetes mellitus aged 6-17 years. Opinions on forearm sampling were collected by questionnaire. RESULTS: Blood glucose results obtained from forearm sampling correlated well with results from the finger measured by the Yellow Springs Instrument analyser. Error grid analysis showed that 100% of measurements were clinically acceptable; 61% of children reported that forearm testing was painless and 19% that it was less painful than finger prick testing. CONCLUSION: Forearm testing is an acceptable alternative to finger prick testing for blood glucose measurement in children and adolescents.     

Neonatal hypoglycaemia in infants of diabetic mothers

OBJECTIVE: To determine whether umbilical cord blood glucose correlates with subsequent hypoglycaemia after birth in infants of well-controlled diabetic mothers. METHODOLOGY: Thirty-eight term infants of well-controlled diabetic mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33 gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal blood glucose was maintained between 4 and 8 mmol/L during labour and delivery. Infants' plasma glucose levels were measured from venous cord blood and serially, at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood glucose levels were further monitored by bedside Dextrostix for 24 h. RESULTS: Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2 mmol/L) during the first 2 h of life. There was no difference in the cord blood glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5 +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10 vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly higher birthweight, and were more likely to be born to Caucasian mothers and by Caesarean section. Raised maternal fructosamine blood level, the need for insulin treatment or the infant's haematocrit were not different between infants with or without hypoglycaemia. CONCLUSIONS: In well-controlled diabetic mothers, the incidence of early hypoglycaemia in infants is still high, particularly in those mothers who had a longer duration of diabetes. Cord blood glucose level did not identify the infants with hypoglycaemia.     

Evaluation of "point of care" devices in the measurement of low blood glucose in neonatal practice

BACKGROUND: Low blood glucose in newborns is difficult to detect clinically. Hence a reliable "point of care" device (glucometer) for early detection and treatment of low glucose is needed. OBJECTIVE: To evaluate the performance of five readily available glucometers for the detection of low blood glucose in newborn infants. METHOD: Glucostix measurements were taken for newborns with risk factors using a Reflolux S (Boehringer) glucometer. If the initial reading was low (< 2.6 mmol/l), further measurements were taken with two other glucometers (phase I, Advantage and Glucotrend (Roche); phase II, Elite XL (Bayer) and Precision (Abbott)), and plasma glucose was measured in the laboratory (Aeroset; Abbott). RESULTS: Over 10 months, 101 specimens were collected from 71 newborns (57 in phase I; 44 in phase II). The Advantage glucometer usually overestimated blood glucose with a mean difference of 1.07 mmol/l (p < 0.01) at all low glucose ranges. The Glucotrend, Precision, and Elite XL glucometers performed better; the mean differences were not significantly different from the laboratory measured value (0.17 mmol/l (p = 0.37); -0.12 mmol/l (p = 0.13), and 0.24 mmol/l (p = 0.13) respectively). For detection of glucose concentrations < 2.6 mmol/l, the Precision glucometer had the highest sensitivity (96.4%) and negative predictive value (90%). For lower glucose concentrations (< 2.0 mmol/l), the Glucotrend glucometer performed even better (sensitivity 92.3%, negative predictive value 96.3%). CONCLUSION: Point of care devices should have good precision in the low glucose concentration range, sensitivity, and accuracy for early detection of neonatal hypoglycaemia. None of the five glucometers was satisfactory as the sole measuring device. The Glucotrend and Precision glucometers have the greatest sensitivity and negative predictive value. However, confirmation with laboratory measurements of plasma glucose and clinical assessment are still of the utmost importance.     

Venous and Capillary Hematocrit in Newborn Infants and Placental Transfusion

Hematocrit values were measured on one hundred and eleven sets of capillary (from unwarmed and warmed heels) and venous blood samples obtained simultaneously during the first 5 days of life from 60 full term newborn infants, 40 of which the umbilical cords were clamped late, and 20 clamped early a t the time of birth. In the late clamped infants, the capillary hematocrits showed an initial rise during the first 6 hours of life seemingly due to fluid transudation in the capillary beds, followed by a fall a t 12 to 24 hours of age due to a subsequent fluid reabsorption into the vascular space in response to increasing circulatory demands in the visceral organs. In the early clamped infants, the capillary hematocrits remained stable during the first 6 hours, but a slight decline was observed a t 12 to 24 hours of age. The simultaneously measured venous hematocrits of both late and early clamped infants plotted against age revealed a strikingly similar pattern of alterations. A marked capillary venous hematocrit difference was observed in the late clamped infants and to a much lesser extent in the early clamped infants during the first 5 days of life, with the venous being lower than the capillary values. Warming the heels prior to capillary sampling improves the capillary venous hematocrit correlations in the late clamped infants and the improvement achieved by this procedure increases as the infant becomes older. In the early clamped infants heel warming produces relatively less effects because there was less capillary venous hematocrit discrepancy initially. In infants over 12 hours of age where venipuncture is difficult or inadvisable, capillary blood samples obtained from warmed heels could be used for hematocrit measurements. However, the hematoples do not exactly correspond with the venous values and the approximate venous reading could be estimated by using the regression lines derived from our samples, and their 95% confidence limit could be calculated from the appropriate formulas.