Direct Ion-selective Electrode Research Articles

Reverse pseudohyperkalemia and pseudohyponatremia in a patient with B-cell non-Hodgkin lymphoma

ObjectivesInvestigate concomitant and spurious high potassium and low sodium results in heparinized plasma. MethodsPotassium and sodium values were measured from heparinized plasma and serum in a patient with B-cell non-Hodgkin lymphoma using both an automated chemistry analyzer (indirect ion selective electrode) and blood gas analyzer (direct ion selective electrode). ResultsPotassium levels were significantly increased while sodium levels were significantly decreased in heparinized plasma compared to serum on several occasions. ConclusionsTo our knowledge, concomitant reverse pseudohyperkalemia and pseudohyponatremia has not been reported previously. We postulate the discrepancy between plasma and serum sodium (pseudohyponatremia in plasma) may be unique to cases of reverse pseudohyperkalemia with extreme potassium elevations.

Vecuronium- and Esmolol-Induced Pseudohypernatremia Due to Drug Interference With Ion-Selective Electrodes

Objectives:We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry analyzer as part of the basic metabolic panel (Vitros 5600; Ortho Clinical Diagnostics, Raritan, NJ), but not by blood gas analyzers (RAPIDLab 1265; Siemens, Tarrytown, NY). Both instruments use direct ion-selective electrode technology, albeit with different sodium ionophores (basic metabolic panel: methyl monensin, blood gas: glass). We questioned if the basic metabolic panel hypernatremia represents artefactual pseudohypernatremia.Design:We added vecuronium bromide or esmolol hydrochloric acid to pooled plasma samples and compared sodium values measured by both methodologies. We queried sodium results from the electronic medical records of patients admitted at Children’s Hospital of Philadelphia from 2016 to 2018 and received vecuronium and/or esmolol infusion treatment during their admissions.Setting:PICU of a quaternary, free-standing children’s hospital.Patients:Children admitted to the hospital who received vecuronium and/or esmolol infusion.Measurements and Main Results:Sodium was measured in pooled plasma samples by basic metabolic panel and blood gas methodologies after adding vecuronium bromide or esmolol hydrochloric acid, leading to a dose-response increase in basic metabolic panel sodium measurements. A repeated measures regression analysis of our electronic medical records showed that the vecuronium dose predicted the Δ sodium (basic metabolic panel–blood gas) sodium within 12 hours of the vecuronium administration (p < 0.0018). Esmolol showed a similar trend (p = 0.13). This occurred primarily in central line samples with continuous vecuronium or esmolol infusions.Conclusions:Vecuronium and esmolol can falsely elevate direct ion-selective electrode sodium measurements on Vitros chemistry analyzers. Unexpectedly high sodium measurements in patients receiving vecuronium and/or esmolol infusions should be further investigated with an alternate sample type (i.e., peripheral blood) or measurement methodology (i.e., blood gas) to guide treatment decisions.

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.

Estimates of blood plasma water content using portable NMR relaxometry

Although blood plasma water content (PWC) is a relevant metric for many medical diagnostic procedures, the routine clinical measurement of PWC has remained elusive. Portable nuclear magnetic resonance (NMR) offers one way to nondestructively and quickly measure PWC. Contrived pseudoplasma samples that mimic blood plasma while also allowing rigorous control over water content are used to demonstrate the role of NMR in this work. Calibration curves relating measured NMR relaxation time constants (T2 and T1) to gravimetric PWC values for a set of human lyophilized plasma samples are used to predict the PWC in porcine and model human blood plasma from respective NMR T2 and T1 values. It is shown that the T2 and T1 decay constants measured with low field NMR relaxometry correlate with the PWC values for pseudoplasma and human lyophilized plasma samples. Statistical testing of the NMR-PWC correlation model demonstrated a prediction accuracy exceeding 98%. The PWC obtained in this way was used to correct sodium cation concentrations reported from direct ion-selective electrode tests. The accuracy of PWC determination with NMR is comparable to that of the gravimetric method that requires sample lyophilization. The rapid turnaround time, non-destructive nature, and portable footprint of the NMR-PWC measurement makes rapid, point-of-care clinical electrolyte estimates possible.

Evaluation of the analytical performance of a portable ion-selective electrode meter for measuring whole-blood, plasma, milk, abomasal-fluid, and urine sodium concentrations in cattle

A portable ion-selective electrode (ISE) meter (LAQUAtwin B-722; Horiba Instruments Inc., Irvine, CA) is available for measuring the sodium ion concentration ([Na]) in biological fluids. The objective of this study was to characterize the analytical performance of the ISE meter in measuring [Na] in whole-blood, plasma, milk, abomasal fluid, and urine samples from cattle. Method comparison studies were performed using whole-blood and plasma samples from 106 sick calves and 11 sick cows admitted to a veterinary teaching hospital, 80 milk and 206 urine samples from 16 lactating Holstein-Friesian cows with experimentally induced free water, electrolyte, and acid-base imbalances, and 67 abomasal fluid samples from 7 healthy male Holstein-Friesian calves fed fresh milk with or without an oral electrolyte solution. Deming regression and Bland-Altman plots were used to determine the accuracy of the meter against reference methods. The meter used in direct mode on undiluted samples measured whole-blood [Na] 9.7 mmol/L (7.3%) lower than a direct ISE reference method and plasma [Na] 16.7 mmol/L (12.7%) lower than an indirect ISE reference method. The meter run in direct mode measured milk [Na] 3.1 mmol/L lower and abomasal fluid [Na] 9.0% lower than indirect ISE reference methods. The meter run in indirect mode on diluted samples accurately measured urine [Na] compared with an indirect ISE reference method. We conclude that, after adjustment for the bias determined from Bland-Altman plots, the LAQUAtwin ISE meter provides a clinically useful and low-cost cow-side instrument for measuring [Na] in whole blood, plasma, milk, and abomasal fluid.

A Study Comparing Values of Serum Potassium Estimated by Colorimetric KIT Method with those Obtained by Direct and Indirect ION Selective Electrode Methods

A Study Comparing Values of Serum Potassium Estimated by Colorimetric KIT Method with those Obtained by Direct and Indirect ION Selective Electrode Methods

Pseudohyponatremia in the Setting of Hypercholesterolemia

To describe a case of pseudohyponatremia in the setting of hypercholesterolemia. A 69-year-old man was admitted to the hospital after asymptomatic hyponatremia was detected on follow-up blood work for acute, drug-induced cholestatic hepatitis. Plasma sodium (PNa) was 119 mmol/L and total protein was 4.7 g/dL. Plasma osmolality was 283 mOsm/kg, urine osmolality was 332 mOsm/kg, and random urine sodium was 45 mmol/L. Pseudohyponatremia was suspected and lipid profiling showed triglycerides were 281 mg/dL, cholesterol was 1,340 mg/dL, high-density lipoprotein was 21 mg/dL, and low-density lipoprotein was 1,419 mg/dL. Direct ion-selective electrode (ISE) using a blood gas analyzer revealed a PNa level of 132 mmol/L. PNa concentration can be measured using direct or indirect ISE. With indirect ISE, the sample is diluted before analysis and the PNa is measured with the assumption that plasma is composed of 93% water. When hyperlipidemia is present, the actual plasma water fraction is decreased, and therefore using indirect ISE will result in falsely low PNa levels. Direct ISE analyzes the sample without dilution. Thus, the PNa is measured directly irrespective of plasma water fraction and so is not affected by changes in plasma percentage concentration. Around two thirds of laboratories in the United States use indirect ISE. Awareness of pseudohyponatremia is important to prevent inappropriate management.

Discrepancy in Chloride Measurement with Decreasing Bicarbonate Concentrations.

Accurate chloride measurement is important in critically ill patients. Chloride concentration measured simultaneously between the central laboratory (indirect ion-selective electrode) and blood gas analysis (direct ion-selective electrode) were compared. We report a discrepancy with chloride measurement between the central laboratory and blood gas analysis at low bicarbonate levels. Caution should be applied while interpreting the chloride concentration when indirect ion-selective electrode methodology is used, especially in the setting of low serum bicarbonate levels.

Evaluation of a portable ion-selective electrode meter for measuring potassium concentrations in whole blood and plasma of calves

An ion-selective electrode (ISE) handheld meter (LAQUAtwin B-731; Horiba) has recently become available for the measurement of potassium concentrations [K+] in biological fluids. The ISE meter has the potential to facilitate the diagnosis and treatment of potassium balance disorders of critically ill cattle. The objective of this study was to characterise the analytical performance of the ISE meter in a study sample of hospitalised calves with a broad range of plasma [K+]. For the purpose of the study, whole blood and plasma samples from 125 calves (age≤3months) were used for analysis. The accuracy of the meter against the reference method (indirect ISE, Cobas c 311, Roche) was assessed using Passing–Bablok regression and Bland–Altman plots.The [K+] in whole blood as measured by the ISE meter in direct mode ranged from 2.4 to 9.9mmol/L. The meter measured whole blood [K+] as 3.8% higher than plasma [K+]. Passing–Bablok regression for whole blood [K+] measured by the meter against plasma [K+] determined by indirect potentiometry revealed a linear relationship that was almost identical to the line of identity. However, the Bland–Altman plot indicated that the meter measured plasma [K+] 5.1% lower than the reference method. This result was consistent with analytical differences of direct and indirect ISE methods in respect to variation in the plasma protein concentration. In conclusion, the LAQUAtwin B-731 meter provides an accurate, rapid and low-cost tool for the diagnosis of potassium derangements in critically ill calves, particularly when whole blood samples are analysed.

Quantitative susceptibility mapping and 23 Na imaging-based in vitro characterization of blood clotting kinetics.

Blood clotting is a fundamental biochemical process in post-hemorrhagic hemostasis. Although the varying appearance of coagulating blood in T1 - and T2 -weighted images is widely used to qualitatively determine bleeding age, the technique permits only a rough discrimination of coagulation stages, and it remains difficult to distinguish acute and chronic hemorrhagic stages because of low T1 - and T2 -weighted signal intensities in both instances. To investigate new biomedical parameters for magnetic resonance imaging-based characterization of blood clotting kinetics, sodium imaging and quantitative susceptibility mapping (QSM) were compared with conventional T1 - and T2 -weighted imaging, as well as with biochemical hemolysis parameters. For this purpose, a blood-filled spherical agar phantom was investigated daily for 14days, as well as after 24days at 7T after initial preparation with fresh blood. T1 - and T2 -weighted sequences, a three-dimensional (3D) gradient echo sequence and a density-adapted 3D radial projection reconstruction pulse sequence for 23 Na imaging were applied. For hemolysis estimations, free hemoglobin and free potassium concentrations were measured photometrically and with the direct ion-selective electrode method, respectively, in separate heparinized whole-blood samples along the same timeline. Initial mean susceptibility was low (0.154±0.020ppm) and increased steadily during the course of coagulation to reach up to 0.570±0.165ppm. The highest total sodium (NaT) values (1.02±0.06 arbitrary units) in the clot were observed initially, dropped to 0.69±0.13 arbitrary units after oneday and increased again to initial values. Compartmentalized sodium (NaS) showed a similar signal evolution, and the NaS/NaT ratio steadily increased over clot evolution. QSM depicts clot evolution in vitro as a process associated with hemoglobin accumulation and transformation, and enables the differentiation of the acute and chronic coagulation stages. Sodium imaging visualizes clotting independent of susceptibility and seems to correspond to clot integrity. A combination of QSM and sodium imaging may enhance the characterization of hemorrhage.

Comparison Between Measured and Calculated Free Calcium Values at Different Serum Albumin Concentrations.

Introduction:Free ionic calcium is the metabolically active component of total calcium (TCa) in blood. However, most laboratories report TCa levels that are dependent on serum albumin concentration. Hence, several formulae have evolved to calculate free calcium levels from TCa after adjustment for albumin. However, free calcium can directly be measured using direction selective electrodes rather than spectrophotometric methods used in autoanalyzers.Objectives:This study compares the levels of free calcium obtained by measurement by direct ion selective electrode (ISE) and the one calculated as a function of TCa by formulae.Materials and Methods:A total of 254 serum samples submitted to clinical biochemistry laboratory of a tertiary care hospital were analyzed for total protein, albumin, and TCa by standard spectrophotometric methods and for free calcium by direct ISE. Three commonly used formulae viz. Orrell, Berry et al. and Payne et al. were used to calculate adjusted TCa. Calculated free calcium was obtained by taking 50% of these values.Results:A significant difference (P < 0.05) was observed between calculated free calcium by all the three formulae and measured free calcium estimated by direct ISE using paired t-test and Bland–Altman plots.Conclusion:Formulae for predicting free calcium by estimating TCa and albumin lacks consistency in prediction and free calcium should be evaluated by direct measurement.

Are sodium and potassium results on arterial blood gas analyzer equivalent to those on electrolyte analyzer?

Objectives:The present study was conducted with the aim to compare the sodium (Na) and potassium (K) results on arterial blood gas (ABG) and electrolyte analyzers both of which use direct ion selective electrode technology.Materials and Methods:This was a retrospective study in which data were collected for simultaneous ABG and serum electrolyte samples of a patient received in Biochemistry Laboratory during February to May 2015. The ABG samples received in heparinized syringes were processed on Radiometer ABL80 analyzer immediately. Electrolytes in serum sample were measured on ST-100 Sensa Core analyzer after centrifugation. Data were collected for 112 samples and analyzed with the help of Excel 2010 and Statistical software for Microsoft excel XLSTAT 2015 software.Results:The mean Na level in serum sample was 139.4 ± 8.2 mmol/L compared to 137.8 ± 10.5 mmol/L in ABG (P < 0.05). The mean difference between the results was 1.6 mmol/L. Mean K level in serum sample was 3.8 ± 0.9 mmol/L as compared to 3.7 ± 0.9 mmol/L in ABG sample (P < 0.05). The mean difference between the results was 0.14 mmol/L. Statistically significant difference was observed in results of two instruments in low Na (<135 mmol/L) and normal K (3.5-5.2 mmol/L) ranges. The 95% limit of agreement for Na and K on both instruments was 9.9 to −13.2 mmol/L and 0.79 to −1.07 mmol/L respectively.Conclusions:The clinicians should be cautious in using the electrolyte results of electrolyte and ABG analyzer in inter exchangeable manner.

A Study on Effect of Lipemia on Electrolyte Measurement by Direct Ion selective Electrode Method

Background: Lipemia affects electrolyte concentration obtained by indirect ion selective electrode (ISE) method, but the specific influence on measurements by direct ion selective electrode method is yet to be clearly understood. A study was designed in this backdrop to assess possible role of escalating concentration of lipemia on electrolyte measurement by direct ISE. Methods: Samples were collected from selected subjects in a hospital setting. A predesigned pretested format was used for recording the data from each subject. Serum sample was divided into 5 aliquots. Except for one, in the rest four, intralipid was added in escalating concentration to induce lipemia. The 5 sub-samples were tested for electrolytes and lipid concentration in parallel by two different direct ion-selective electrode methods, namely VITROS250 & HDC-Lyte. Electrolytes like sodium & potassium concentration was measured by both, while the first one also measured triglyceride concentration. Result: Results from two instruments were compared and data were also analsyed in subgroups of standard clinical classification for sodium concentration. Considering 0-350 mg% of triglyceride as the reference, electrolytes concentration mostly decreased over increasing lipemia. Beyond triglyceride concentration of 650mg%, this decline in electrolytes concentration was statistically significantly for samples in all subgroups. In majority of samples, electrolyte values obtained from two instruments were comparable. Beyond triglyceride concentration of 1550 mg%, the sodium concentration obtained from two instruments varied significantly. Conclusion: A correction factor may be used for the amendment of this interference property of lipemic serum samples for the major electrolytes i.e., sodium and potassium.

Flame Photometer and Direct Ion-Selective Electrode on Serum Sodium and Potassium Concentration

The study aimed to compare the Na+ and K+ serum levels of the blood samples using flame photometry and ion-selective electrode methods. The study was conducted using the descriptive and comparative design.  By random sampling, the values of the 180 test samples were extracted from the Chemistry Clinical logbook. The mean values and paired t-test were used to treat the data gathered. The mean value of Na+ serum of the 180 blood samples using flame photometry and ISE are 136.96 (SD = 6.21) and 138.32 (SD = 6.21) respectively. The potassium mean values are 3.77 (SD = 0.83) for the flame photometry and 3.84 (SD=0.86) for the ISE. The t-values resulted to p-values, which are lesser than 0.05, indicating that there is a significant difference between the electrolyte values of both sodium and potassium using the flame photometer and ion-selective electrodes. The ion-selective electrode outweighs the flame photometer in determining the electrolytes particularly sodium and potassium in serum.  Keywords: Flame photometer, ion-selective electrode, serum electrolytes

Reference Intervals of Serum Sodium, Potassium, and Chlorine in Chinese Han Population and Comparison of Two ISE Methods.

Currently there are no reference intervals (RIs) of sodium (Na), potassium (K), and chlorine (Cl) on Chinese population. Two kinds of ion-selective electrode (ISE) methods were commonly used to determine K, Na, and Cl levels in China, the difference between these two methods needs to be evaluated. A total of 4,524 healthy participants (1,916 males and 2,608 females) between 20-79 years old from six cities in China were selected by strict criteria. Serum K, Na, and CL were tested on Roche Modular analyzers in six assigned laboratories. According to EP-9A2, using Roche Modular analyzer (indirect ISE) as comparative method, Olympus AU 5400 analyzer (indirect ISE) and Johnson&Johnson Fusion 5.1 analyzer (direct ISE) were evaluated. In Chinese population, the RIs for K, Na, and CL are 3.6-5.2, 136-146, and 99-110 mmol/l, respectively. Compared to the Roche indirect ISE method, Johnson direct ISE method showed a positive bias; and Olympus indirect ISE method just showed a very slight bias. The RIs of K, Na, and Cl of Han Chinese healthy adult population were found to be smaller than those provided by the manufacturer. By a criteria of biological variations for CV, the differences of Na and K between Roche analyzer and Johnson analyzer were not acceptable for clinical application, while the differences of Na, K, and Cl between Roche and Olympus analyzers were acceptable for clinical application.

Case study : spurious elevation of sodium levels : peer reviewed case study

In hospitalized patients, plasma sodium disturbances remain common and can be associated with significant mortality and morbidity if not diagnosed and treated. A hypoproteinaemic, critically ill patient with discrepant blood gas analyzer and central laboratory analyzer sodium values presented as a case of possible spurious elevation of sodium or pseudohypernatraemia. The indirect ion selective electrode method yielded a persistently higher sodium value than the direct ion selective electrode method. A statistically significant difference between the sodium measured with the direct ISE and indirect ISE method was noted. The differences could not be explained by analytical variation alone, in most of the samples.

Effect of albumin and total protein concentration on plasma sodium measurements in the ICU

Direct ion-selective electrode without dilution is the most effective method for determination of the concentration of the ionized fraction of sodium [1]. We tested the hypothesis that the difference between indirect and direct sodium assays would be related to the plasma albumin concentration or the total protein concentration.

Multiple lipoprotein and electrolyte laboratory artifacts caused by lipoprotein X in obstructive biliary cholestasis secondary to pancreatic cancer

Lipoprotein X (Lp-X) is an abnormal lipoprotein which may form in patients with intra- and extra-hepatic cholestasis. The presence of very high levels of Lp-X has been shown to be a rare cause of pseudohyponatremia. We present a patient with severe obstructive cholestasis secondary to pancreatic cancer leading to very high Lp-X concentrations resulting in pseudohyponatremia, pseudohypokalemia, pseudohypochloremia and interference with the selective micellary solubilization direct low density lipoprotein cholesterol assay. These spurious laboratory anomalies impeded the initial clinical management of the patient including the attempted correction of the electrolyte abnormalities. After relief of obstruction following biliary stent placement, the patient's lipid levels normalized. Clinicians must be wary of laboratory artifacts and remember to correlate the laboratory values with the clinical presentation of the patient. Assays employing direct ion-selective electrodes such as those in blood gas analyzers are not subject to the interference of high concentrations of lipids or proteins, and maybe useful in situations where such interference is suspected. Furthermore the Vertical Auto Profile (VAP®) ultracentrifugation assay may be useful to detect lipoprotein X and low density lipoprotein cholesterol levels when the selective micellary solubilization technique fails to detect or quantify these lipid moieties.

Pseudohyponatremia revisited: a modern-day pitfall.

Abstract Factitiously low sodium estimations are a hazard in most modern clinical laboratories. Most modern high-throughput analyzers use indirect ion-selective electrodes to estimate electrolyte concentrations in serum samples. This analysis is preceded by a dilution step of the sample. If the water concentration is altered by the presence of increased lipid or protein, the dilution step and the subsequent calculation of concentration by the analyzer results in a falsely low sodium value. This places patients at risk, particularly if the factitious result is acted upon by the physician. In this short review, we highlight this problem and review the methodology and situations where this artifact can occur and discuss strategies to circumvent this problem. When factitious results are suspected, whole blood sodium can be assessed using a direct ion-selective electrode, by measurement of osmolality, or by calculation of the serum water fraction and applying a correction to the reported value.

Pseudohyponatremia Revisited: A Modern-Day Pitfall

Factitiously low sodium estimations are a hazard in most modern clinical laboratories. Most modern high-throughput analyzers use indirect ion-selective electrodes to estimate electrolyte concentrations in serum samples. This analysis is preceded by a dilution step of the sample. If the water concentration is altered by the presence of increased lipid or protein, the dilution step and the subsequent calculation of concentration by the analyzer results in a falsely low sodium value. This places patients at risk, particularly if the factitious result is acted upon by the physician. In this short review, we highlight this problem and review the methodology and situations where this artifact can occur and discuss strategies to circumvent this problem. When factitious results are suspected, whole blood sodium can be assessed using a direct ion-selective electrode, by measurement of osmolality, or by calculation of the serum water fraction and applying a correction to the reported value.