Method-dependent Variation in Serum Electrolytes: A Cross-sectional Study Comparing Direct and Indirect Ion-selective Electrodes

Introduction: Serum electrolyte measurement, particularly sodium, potassium, and chloride, is among the most commonly ordered investigations in routine and emergency care. Rapid and accurate reporting is essential for timely clinical decisions. Most modern electrolyte analysers utilise Ion-selective Electrode (ISE) technology, available in two forms: direct ISE (dISE), which measures electrolytes in undiluted serum, and indirect ISE (iISE), which measures them after pre-dilution. These methodological differences may influence reported values. Aim: To compare the serum sodium, potassium, and chloride levels measured using dISE versus iISE methods. Materials and Methods: The cross-sectional study was conducted in the Clinical Biochemistry Laboratory, Government Medical College and Hospital, Chandigarh, India, from March 2024 to and June 2024. A total of 150 serum samples were obtained from the outpatients, inpatients, and Intensive Care Unit (ICU) patients. Paired serum samples available for simultaneous direct and iISE estimation were included. Deidentified residual samples were analysed and assigned a unique code. dISE was performed using the ABL800 FLEX (Radiometer) on undiluted serum, while iISE was performed using the Beckman Coulter AU5800 on prediluted serum; both followed the manufacturer’s calibration and two-level internal Quality Control (QC) protocols. Testing order was randomised, and paired measurements were completed within 30-60 minutes to avoid analyte instability. Statistical analysis included Bland–Altman plots to assess agreement and Spearman’s correlation to evaluate the association between the two methods. Analysis was stratified by clinically relevant electrolyte ranges, with p<0.05 considered statistically significant. Results: dISE yielded significantly higher sodium and chloride levels than iISE. Subgroup analysis using clinically relevant thresholds demonstrated significant correlations for serum sodium ≤140 mEq/L, potassium ≥4.5 mEq/L, and chloride levels across both concentration groups (>103 and <103 mEq/L), with correlation coefficients of r=0.546, 0.870, 0.602, and 0.703, respectively (p<0.0001). Conclusion: A significant difference was observed between dISE and iISE methods for serum electrolyte measurement, particularly within specific clinical ranges. These findings highlight the need for methodological consistency in electrolyte analysis, especially in emergency and critical care settings, to prevent misinterpretation and inappropriate clinical decisions arising from analytical variability.