B-154 Characterizing Ability of the Serum Potassium (K) to Flag Hypokalemia or Hyperkalemia as Observed in Plasma: A Simulation Study
Authors: Stickle D F , Koob K R , McCudden C R 
Published: September 2023

Abstract

Background
Plasma has long been the recommended specimen type for K measurement. However, serum usage persists, including use due to recent plasma tube shortages. In comparison to plasma K, serum K is generally right-shifted (higher). This shift varies across individual samples according to a normal distribution. Consequentially, K results outside of the population reference interval (RI) for plasma (hypokalemia or hyperkalemia) are unlikely to be strictly concordant with classification in serum according to the serum RI. Serum may thus have a lower sensitivity to detect either hypokalemia or hyperkalemia relative to plasma. We examined this premise from a theoretical standpoint by simulation.

Methods
We used longstanding and widely implemented textbook K reference intervals (Tietz, 4th Ed.) for plasma (PRI = 3.4–4.5 mmol/L) and serum (SRI = 3.5–5.1 mmol/L). The difference between plasma K and serum K is characterized by a normally distributed function where serum = plasma + 0.35 ± 0.3 mmol/L. This transformation was applied to an at-large patient data distribution from a large academic medical center to generate a theoretical serum K distribution from real world plasma patient K results. The simulated serum K data were characterized as to whether hypokalemic and hyperkalemic plasma K specimens as defined by PRI were also classified in serum as being either below or above lower and upper limits of SRI, respectively.

Results
Primary data were a plasma K patient distribution for a three month interval (n = 59 570; median = 4.1 mmol/L; hypokalemia = 6.5%; hyperkalemia = 16.7%). Simulated serum K data from the plasma transformation (n = 100 000) yielded a right-shifted distribution (median = 4.4 mmol/L) with 4.1% of results below the lower limit of SRI, and 11.4% of results above the upper limit of SRI. For samples originating as hypokalemic according to the PRI, sensitivity for detection by being flagged as below the lower limit of the SRI was 44.1% (specificity = 98.7%). For samples originating as hyperkalemic according to the PRI, sensitivity for detection by being flagged as above the upper limit of the SRI was 58.7% (specificity = 97.6%).

Conclusions
Simulation results indicate that serum K should best be thought of as an inferior substitute marker for plasma K. Depending on reference intervals employed, sensitivity of serum RI for detection either of plasma hypokalemia or hyperkalemia may be significantly less than 100%. This can result in a significant degree of misidentification of hyperkalemia or hyperkalemia as being within SRI. In our simulation, 55.9% of plasma hypokalemia results were in serum classified as being within the SRI; 41.3% of plasma hyperkalemia results were in serum classified as being within the SRI. Additionally, note that a switch from serum to plasma will likely precipitate a significant increase in flag rates for plasma K outside of the PRI compared to flag rates observed for serum K outside of the SRI. These results follow simply from the fact that serum K includes a random component not present in plasma.