This study shows that a common lab test for sodium can give falsely low results when blood protein levels are unusually high, because the test method (indirect ISE) is affected by the extra protein. Most labs don’t check protein at the same time, so the error can go unnoticed.

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 (<i>a</i>) establish the relationship between serum total protein (TP) concentration and the magnitude of the electrolyte exclusion effect on indirect ISE-measured sodium values (<i>b</i>) estimate the frequency at which TP concentrations outside the reference interval may impact indirect-ISE measured sodium values, and (<i>c</i>) 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 (&#x394;[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. &#x394;[Na⁺] was inversely proportional to TP concentration (y = -1.29x + 8.6, <i>R</i> = -0.883). The average difference (SD, range) was -6.1(3.4, -16-0) mmol/L when TP &gt;7.9 g/dL (&gt;79g/L), with 69% of samples demonstrating differences &#x2265;4.0 mmol/L. A majority of intensive care unit patients (81%) were hypoproteinemic (&lt;6.3 g/dL, &lt;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.