Numerous studies have tried to calculate the correct sodium concentration in patients with hyperproteinemia or hyperlipidemia by using indirect ISE values and the level of proteins, albumin, or triacylgly-cerols in a sample. The methods used in these papers have several shortcomings, however.
What causes discrepancies between results from direct and indirect ion selective electrodes (ISE)?
There are two methods for measuring serum electrolytes using ISE: direct and indirect. As the name suggests, with direct ISE the patient’s serum sample is brought into direct contact with the electrode surface and the activity of the relevant ion is measured in the plasma water of the serum.
Indirect ISE, on the other hand, involves diluting the patient’s serum with a buffer in the range of 1:16 to 1:34 before the sample comes in contact with the ISE membranes. This method then calculates the electrolyte concentration in the diluted sample by assuming that the original sample had a plasma water concentration of 93%. Indirect ISE analyzers use this calculation because electrolytes are distributed only in the aqueous phase of plasma, while dissolved solids—mostly proteins and lipids—typically make up the remaining 7% of a patient’s plasma volume.
However, many illnesses, such as diabetes, liver and kidney disorders, and alcoholism, can raise protein and lipid concentrations in the blood, causing hyperproteinemia and hyperlipidemia, respec-tively. These conditions do not impact direct ISE, but indirect ISE results depend on the content of solids in a sample because of the dilution step. When the volume of plasma solids increases this can lead to falsely low indirect ISE values for serum electrolytes, especially sodium—a phenomenon known as pseudohyponatremia.
What should labs do when incongruous direct and indirect ISE results are likely?
Numerous studies have tried to calculate the correct sodium concentration in patients with hyperproteinemia or hyperlipidemia by using indirect ISE values and the level of proteins, albumin, or triacyl-glycerols in a sample. The methods used in these papers have several shortcomings, however: They either overestimate the drop in sodium levels, involve overly complex calculations, or fail to account for all the parameters comprising the solid phase of plasma.
These algorithms also do not hold true through the entire spectrum of protein and lipid concentrations. Therefore, beyond certain cutoffs for protein and lipid concentrations, the safest bet for laboratories is to report serum electrolyte levels through direct ISE only.
Labs should also educate clinicians about the scenarios in which these two technologies are used and the potential for discrepancies arising between them. Indirect ISE is more commonly used in automated analyzers in the central lab, while direct ISE is usually available at the point of care. Labs should especially discourage clinicians from using results from these two methods inter-changeably, particularly in the setting of critical care monitoring.
Are there potential solutions to this problem on the horizon?
To date, no algorithm has been developed to predict a correct sodium concentration using indirect ISE values and the concentrations of plasma proteins and lipids. One alternative approach that could evolve into a solution is measuring the plasma water concentration in a sample and using this value as a corrective factor instead. This method must be studied further before it can be used in the clinical setting, however.
Sudip Kumar Datta, MBBS, MD, DHM, is an assistant professor in the department of laboratory med-icine at All India Institute of Medical Sciences in New Delhi, India. E-mail: dr.sudipdatta[at]gmail.com