Indirect Indirect Ion Selective Electrode Research Articles

Prevalence and detection of citrate contamination in clinical laboratory.

To study the prevalence of trisodium citrate (Na3Citrate) contamination in hypernatraemic serum samples by direct measurement of citrate and to evaluate the performance of indirect markers for identification of Na3Citrate contamination. Serum citrate was measured in all hypernatraemic serum samples (sodium≥148 mmol/L) over a three-month period. The performance of serum chloride, sodium-chloride gap, indirect ion selective electrode (ISE)-direct ISE sodium disparity and osmolar gap in identification of Na3Citrate contaminated samples was assessed against the 'gold-standard' direct citrate measurement. In total, 27 Na3Citrate contaminated samples were identified based on serum citrate concentration≥1.5 mmol/L. The prevalence of citrate contamination was 3.1 % of hypernatraemic samples (n=875) and 0.017 % of all samples received for urea and electrolyte analysis (n=153,404). Mostcontaminated samples were from patients receiving haemodialysis (59.3 %), and the rest from inpatients. Cut-offs to give 100 % sensitivity were chloride≤105 nmol/L (specificity 93.4 %), sodium-chloride gap≥47 mmol/L (specificity 95.3 %), indirect ISE-direct ISE sodium disparity≥3 mmol/L (specificity 81.9 %), and osmolar gap ≥39mOsm/kg (specificity 2.8 %). Trisodium citrate contamination is uncommon. Most contaminated samples were from patients receiving haemodialysis, likely because of contamination with citrate catheter locking solution. Screening with serum chloride or sodium-chloride gap can confidently exclude Na3Citrate contamination in over 90 % of hypernatraemic samples, and in nearly all samples with sodium≥155 mmol/L if metabolic alkalosis has been excluded. In the remaining samples, Na3Citrate contamination can only be definitively confirmed or excluded by measurement of serum citrate. We propose algorithms to identify spurious hypernatraemia.

Comparing the effect of Hypoalbuminemia on Sodium measured by Indirect versus Direct Ion Selective Electrode Method

Objective: To evaluate the effect of low serum Albumin levels on serum sodium measurement when analyzed by the indirect Ion Selective Electrode (ISE) method and to compare the results with the direct Ion selective electrode (ISE) method.
 Study Design: Cross-sectional study
 Place and Duration of Study: Department of Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Jan to Mar 2021.
 Methodology: Patients of either gender, aged 18 to 70 years, who were admitted to the Intensive Care Unit of Combined Military Hospital, Rawalpindi, were selected. A total of 200 blood samples were collected in a gel tube. Serum samples were analyzed for albumin and sodium within two hours of sample collection. Sodium levels were measured concurrently by both direct and indirect ISE methods. The difference in results between these two techniques was studied.
 Results: Hypoalbuminemia was detected in 176(88%) patients, while 24(12%) had normal albumin levels. In Hypoalbuminemic patients, serum sodium measurements were higher using the indirect ISE method(134.07±5.55) compared to the direct ISE method (130.95±6.04); the difference between the two techniques was statistically significant (p-value <0.001).Pearson correlation coefficient (r-value = -0.86, p-value <0.001) revealed a symmetrical increase in differences between the two methods as the albumin level decreased.
 Conclusion: In Hypoalbuminemic patients, the indirect ISE method gave falsely raised results of serum sodium. In such patients, serum sodium measurement by the Direct ISE method offers more accurate and consistent electrolyte results.

Preventing pseudohyponatremia: Intralipid®-based lipemia cutoffs for sodium are inappropriate

BackgroundPseudohyponatremia describes an artifactual decrease in plasma sodium result in samples with high proteins and/or lipids when measured by an indirect ion-selective electrode (ISE) method. We suspected that Intralipid®-based lipemia cutoffs are inappropriate for detecting interfering lipids in human samples and a major contributing factor to the existence of pseudohyponatremia. MethodsWe evaluated 2 approaches to derive a lipemia cutoff for sodium, one in which patient plasma samples were pooled and spiked to simulate hyperlipidemia using Intralipid® (commonly used approach by in-vitro diagnostics manufacturers), and another in which endogenous hyperlipidemic samples (n = 31) were measured by methods not affected by hyperlipidemia (i.e., direct ISE and post-ultracentrifugation indirect ISE). Triglycerides, lipemic index (L-index) and indirect ISE sodium concentrations of samples were measured on Roche Cobas® 8000 and direct ISE on Radiometer® ABL835 Flex analyzers. Endogenous hyperlipidemic samples were also ultracentrifuged on Beckman Coulter® Airfuge to clear excess lipids and re-analyzed for sodium by indirect ISE. ResultsWe discovered that Intralipid® is not an accurate emulation of the lipemic interference seen in pseudohyponatremia because it showed no effect up to the maximum level of lipemia tested (L-index = 2000). By contrast, endogenous hyperlipidemic samples demonstrated significant deviations in sodium concentration (≥4 mmol/l) when L-index approached or exceeded 700, and a strong positive correlation between L-index and the difference between the indirect and direct methods (i.e., extent of pseudohyponatremia). ConclusionsClinical laboratories should lower their tolerance for lipemia from the currently recommended L-index cutoff of 2000 on Roche Cobas 8000®. We recommend reflexing to direct ISE when L-index exceeds 700. Manufacturers and laboratories with other indirect ISE methods should evaluate the effect of lipid interference on their method using hyperlipidemic human samples not Intralipid®.

Establishment and application of a new serum sodium candidate reference method

BackgroundLevels of serum sodium (Na) are widely determined in clinical laboratories. Accordingly, sodium quantification must be performed using reliable methods. Herein are reported the results of the evaluation of a new inductively coupled plasma mass spectrometry (ICP-MS) method for sodium quantification. MethodsSerum samples were diluted 100 × by 0.3% ultrapure nitric acid, and germanium (Ge) was used as an internal standard. Sodium calibration solutions with different concentrations were added to serum matrix solutions. The serum sodium concentration was calculated according to the standards addition method. The analytical performance of the method, as well as a comparison with other sodium method, was investigated. ResultsThe correlation coefficients (r) between the measured Na/Ge ratios and the analyte concentration ratios were all > 0.9999. Intra- and between-assay coefficients of variation (CVs) were < 0.64% and < 0.57%, respectively, and the total CV was < 0.67%. The trueness of the method was verified by measuring a certified reference material, SRM 956d. The new ICP-MS method was compared with the 2017 and 2018 External Quality Assessment Scheme for Reference Laboratories in Laboratory Medicine (RELA). The results were well correlated with those obtained by the routine indirect ion selective electrode (ISE) method: sodium (ICP-MS, mmol/L) = 0.9895 × sodium (ISE, mmol/L) + 1.3049 (r = 0.9914, n = 40). The mean deviation between the results of the ICP-MS method and the indirect ISE method was –0.15%. ConclusionsThe new ICP-MS method proved to be accurate, reliable, simple, and fast and may be used as a candidate reference method for setting target values in the standardization of serum sodium measurements.

Comparison of two methods for the measurement of serum chloride

Background: Discrepancies in electrolyte concentration, namely sodium and potassium using the direct and indirect ion selective electrode (ISE) methods have been described. The present study was taken up to compare serum chloride values obtained using the direct and indirect ISE methods. Methods: Serum chloride measurement was done in residual samples received in the clinical laboratory using direct ISE method and indirect ISE method. Imprecision, accuracy and comparability of the methods were studied as per the Clinical and Laboratory Standards Institute EPA guidelines. The American Clinical Laboratory Improvement Amendments (CLIA) guideline of acceptability of target ±5% was considered as the quality goal. Results: Both the methods had acceptable imprecision and inaccuracy of Conclusions: The findings of the present study show that serum chloride estimation using direct ISE and indirect ISE methods are comparable.

Prevalence of Clinically Significant Differences in Sodium Measurements Due to Abnormal Protein Concentrations Using an Indirect Ion-Selective Electrode Method.

Indirect ion-selective electrode (ISE) is the primary method used to measure sodium in automated clinical laboratories and is susceptible to the electrolyte exclusion effect. Pseudohyponatremia due to hyperproteinemia can affect patient management. The aims of this study were to (a) establish the relationship between serum total protein (TP) concentration and the magnitude of the electrolyte exclusion effect on indirect ISE-measured sodium values (b) estimate the frequency at which TP concentrations outside the reference interval may impact indirect-ISE measured sodium values, and (c) determine whether clinical decision support (middleware) rules in the laboratory would be effective for detecting cases of pseudohyponatremia. Residual waste serum specimens from physician-ordered TP testing were collected (n = 112). Sodium concentration was measured using indirect ISE (Cobas 8000, Roche Diagnostics) and direct ISE (ABL 825, Radiometer) methods. The difference in sodium concentration (Δ[Na+]) was calculated as follows: ([Na+]indirect-ISE - [Na+]direct-ISE). Retrospective TP results reported from July 31, 2013, to September 24, 2014, were stratified by ordering location and sodium and TP co-ordering rates were quantified. Δ[Na+] was inversely proportional to TP concentration (y = -1.29x + 8.6, R = -0.883). The average difference (SD, range) was -6.1(3.4, -16-0) mmol/L when TP >7.9 g/dL (>79g/L), with 69% of samples demonstrating differences ≥4.0 mmol/L. A majority of intensive care unit patients (81%) were hypoproteinemic (<6.3 g/dL, <63g/L). Only 10.9% of sodium test orders include an order for TP on the same collection. Indirect sodium measurement is impacted when TP concentrations are increased. TP concentration outside the reference interval is prevalent and sodium is usually not ordered with TP. Health systems need to be aware of the limitations of their indirect-ISE method for sodium measurement.

Is spectrophotometric enzymatic method a cost-effective alternative to indirect Ion Selective Electrode based method to measure electrolytes in small clinical laboratories?

Abstract Aim Our study was aimed to compare two different laboratory methods used to measure serum sodium and serum potassium level i.e. between the indirect Ion Selective Electrode (ISE) based and Enzymatic based method in Beckman Coulter AU-480, USA, in serum samples. Materials and methods This was a cross sectional single center study carried out from September’16 to January’17 on 130 serum samples, to compare the result of serum sodium (S. Na+) and serum potassium (S. K+) level by indirect ISE and Enzymatic method in fully automated biochemistry analyzer (Beckman Coulter AU-480, USA). Results To validate new enzymatic method bias, CV% and correlation coefficient were measured for S. Na+ and S. K+. The study has drawn a considerable agreement for measurement of S. K+ level between two methods with mean ± SD of difference was 0.14 ± 0.22 (p = 0.2242), CV% 2.7% and r2 value of 0.94, whereas disagreement for measurement of S. Na+ level with mean ± SD of difference was 2.38 ± 2.36 (p &lt; 0.01), CV% 0.5% and r2 value of 0.82. Bias, CV% and correlation coefficient are acceptable for S. K+, whereas nonacceptable for S. Na+ level measurement as per Clinical Laboratory Improvement Amendments (CLIA) guidelines. Conclusion There was a good correlation in S. K+ between both methods whereas values were not correlated well with S. Na+ level. So, enzymatic method can be used as an alternative to indirect ISE method for estimation of S. K+ in small laboratories due to its cost effectiveness, but still intense workout is required for estimation of S. Na+.

Interchangeability of Sodium and Potassium Result Values of Arterial Blood Gas with Laboratory Analyzer: Narrative Review.

ABSTRACTThe major extracellular electrolytes, sodium, and potassium are often requested together and form a large percentage of the requested tests in routine clinical chemistry laboratories. Two types of devices that use direct and indirect ion-selective electrode (ISE) methods are used in hospitals for electrolyte measurements: blood gas analyzers (BGA), which use direct ISE technology, and the indirect ISE method, which is often used in a central-laboratory autoanalyzer (AA).We aimed to summarize the current scientific knowledge based on whether the electrolyte test results, using Na and K test results obtained with BGA and an AA, can be used interchangeably.We searched Medline (PubMed), Google Scholar, and Web of Science up to 31st March 2018. In addition, references of the included studies were also examined.Fourteen studies with a risk of bias were included in the analysis. Limits of agreement differences were variable among BGA and AA sodium and potassium test results in clinical practice.The results of both BGA and AA measures should not be used interchangeably under the assumption that they are equivalent to each other.How to cite this articleUstundağ Y, Huysal K, Ozgunay ŞE, Turkoğlu AR. Interchangeability of Sodium and Potassium Result Values of Arterial Blood Gas with Laboratory Analyzer: Narrative Review. Indian Journal of Critical Care Medicine, January 2019;23(1):35-42.

Prevalence of pseudonatremia in a clinical laboratory - role of the water content.

Sodium concentration is a frequently used marker to discriminate between differential diagnoses or for clinical follow-up. Pseudonatremia, as a result of indirect ion-selective electrode (ISE) measurements in automated chemistry analyzers, can lead to incorrect diagnosis and treatment. We investigated whether the estimated water content, based on total protein and lipid concentrations, can be used to reduce diagnoses of pseudonatremia. Indirect and direct ISE measurements of sodium were compared in blood samples from intensive care unit (ICU) (n = 98) and random non-ICU patients (n = 100). Differences between direct measurements using whole blood and lithium-heparin plasma were also determined. Water content, estimated by a linear combination of total protein and lipid concentrations, was used to correct indirectly measured sodium concentrations. The prevalence of pseudonatremia was evaluated in the ICU patient group. An absolute difference of 3 mmol/L was observed between direct measurements using lithium-heparin plasma and whole blood, with higher concentrations in plasma. Additionally, we observed that differences between indirect and direct measurements displayed a linear relationship with the estimated water content. The prevalence of pseudohypernatremia after indirect measurements (32%) was reduced when measurements were corrected for water content (19%). In critically ill patients, sodium concentrations should be preferably measured by direct measurements. Whole blood is the preferred material for these measurements. For routine sodium analyses in other patients, correction using the estimated water content appears promising in reducing the prevalence of pseudohypernatremia by indirect measurements.

Plasma sodium measurements by direct ion selective methods in laboratory and point of care may not be clinically interchangeable.

An estimated 25% of indirect ion selective electrode (ISE) ICU plasma sodium measurements differ from corresponding direct ISE values by at least 4mmol/L, the dominant factor being indirect ISE over-estimation driven by hypoproteinemia. Since direct measurements are considered unaffected by protein concentrations, we investigated whether direct ISE plasma sodium measurements in the laboratory and at point of care in ICU show sufficient agreement to be clinically interchangeable. From a 5year clinical chemistry database, 9910 ICU plasma samples were assessed for agreement between direct ISE sodium measurements in ICU (ABL 700) and in the central laboratory (Vitros Fusion). The relationship between differences in paired plasma sodium measurements (Vitros-ABL) and total plasma protein concentrations was evaluated by generalized estimating equation linear regression. Patients were hypo-proteinemic [mean (SD) total protein concentration 56.9 (9.04)g/L]. Mean (SD) paired Vitros-ABL sodium measurements was -0.087 (1.74) mmol/L, range -14 to +10mmol/L. Disagreement at ≥|4|mmol/L, ≥|3|mmol/L and ≥|2|mmol/L was present in 409 (4.1%), 1333 (13.4%) and 3591 (36.2%) pairs respectively. Test-retest disagreement estimates within either source alone were substantially lower. Small negative Vitros-ABL differences associated with low plasma protein concentrations were reversed at high protein concentrations. Disagreement between plasma sodium concentrations monitored by two common direct ISE analyzers was substantially less than reported between direct and indirect ISE devices, although a protein influence of low clinical importance persisted. Disagreement was sufficient to jeopardize safe interchangeable interpretation in situations with a low tolerance for imprecision, such as hyponatremia correction.

Disagreement between ion selective electrode direct and indirect sodium measurements: Estimation of the problem in a tertiary referral hospital

PurposeWe estimated the proportion of indirect ion selective electrode (ISE) plasma sodium analyses in intensive care unit (ICU) and hospital wide, exhibiting important disagreement with direct ISE results in relation to abnormal plasma protein concentrations. Materials and MethodsDirect and indirect ISE plasma sodium measurements were performed on 346 clinical specimens selected to reflect low, normal, or high total protein concentrations. Important intermethod disagreement was defined as |4| mmol/L or higher. Results were extrapolated to a 3-month laboratory series of 48 033 indirect ISE assays, including 2877 samples from intensive care. ResultsIntermethod sodium disagreement at |4| mmol/L or higher was predicted for 25% of ICU samples. Almost all (97%) occurred in hypoproteinemic samples where indirect tended to exceed direct ISE estimates. Hospital wide, such disagreement was projected to occur in 8% of samples, of which the majority (70%) were also hypoproteinemic. ConclusionsImportant disagreement between indirect and direct ISE sodium measurements may exist in up to 1 in 4 ICU specimens and 1 in 12 hospital-wide samples. The main problem is indirect ISE overestimation associated with hypoproteinemia, potentially leading to misclassifications of pseudohypernatremia and pseudonormonatremia. We recommend that hospital laboratories consider standardization using direct ISE sodium measurement.

Sodium measurement: effects of differing sampling and analytical methods

It is recommended that children receiving intravenous fluids should have frequent biochemical monitoring, in some situations 4-6 hourly. Small changes in sodium must be detected, requiring very high precision from sodium analyses. Some children are monitored using venous blood analysed by indirect ion-selective electrode (ISE) interchangeably with capillary blood analysed by direct ISE. Our aim was to determine whether variability in sample collection together with variability in sodium measurement would lead to results which were unacceptable in the clinical setting. Fifty-seven adults had capillary and venous blood analysed for sodium using direct ISE and venous plasma analysed for sodium using indirect ISE. Comparison of capillary blood analysed by direct ISE with venous plasma analysed by indirect ISE demonstrated wide scatter and poor correlation of results: r = 0.36, standard deviation (SD) of the differences 2.7 mmol/L and range of limits of agreement 10.6 mmol/L. Significant biases were observed comparing capillary blood sodium with venous plasma sodium (P < 0.001), and comparing direct ISE with indirect ISE (P < 0.001). Venous plasma using indirect ISE and capillary blood with direct ISE cannot be used interchangeably to detect small changes in plasma sodium concentrations. To avoid misinterpretation of results when monitoring sodium over short time periods, the use of single methods of sampling and analysis must be strongly encouraged.

Effects of Hyperlipidemia on Plasma Sodium, Potassium, and Chloride Measurements by an Indirect Ion-Selective Electrode Measuring System

We used indirect ion-selective electrode (ISE) methods (Roche/Hitachi Modular) to investigate the effect of hyperlipidemia (cholesterol plus triglycerides) on measurements of sodium, potassium, and chloride and the ability of published formulas to correct for the decrease in measured Na+, K+, and Cl−. As recommended by Kroll (1), we did not use enriched samples but instead used 21 patient samples (lithium-heparin plasma and serum) with triglyceride concentrations >15 mmol/L, total lipid concentrations (cholesterol plus triglycerides; Roche/Hitachi Modular) >20 mmol/L, a lipemic index (Modular) >3, and a total protein concentration within the reference interval (62–83 g/L). We analyzed samples before and after ultracentrifugation (Airfuge; Beckman Coulter; 15 min at 107 000 g ) by indirect ISE potentiometry (Modular) and direct ISE (Rapidlab 865; Bayer). The ultracentrifuged indirect ISE result ( y ) and nonultracentrifuged direct ISE result ( z ) were subtracted from the nonultracentrifuged indirect ISE result ( x ; see Fig. 1 in the Data Supplement that appears with the online version of this letter at http://www.clinchem.org/content/vol52/issue1/). …