Characterizing ability of serum potassium (K) and the serum K reference interval to flag hypokalemia or hyperkalemia as observed in plasma: A simulation study

Objectives: Serum potassium (K) exhibits a positive shift relative to plasma K due to a variable amount of K release associated with clotting. Because of this variation, plasma K results outside of the reference interval (RI) for plasma (hypokalemia or hyperkalemia) in individual samples may not produce classification-concordant results in serum according to the serum RI. We examined this premise from a theoretical standpoint by simulation. Design & methods: We used textbook K reference intervals for plasma (PRI = 3.4-4.5 mmol/L) and serum (SRI = 3.5-5.1 mmol/L). The difference between PRI and SRI is characterized by a normal distribution: serum K = plasma K + 0.35 & PLUSMN; 0.308 mmol/L. This transformation was applied by simulation to an observed patient data distribution for plasma K to generate a corresponding theoretical serum K distribution. Individual samples were tracked for comparison with respect to classification (below, within, above RI) for plasma and serum. Results: Primary data were an all-comers plasma K patient distribution (n = 41,768; median = 4.1 mmol/L; 7.1% below PRI (hypokalemia); 15.5% above PRI (hyperkalemia)). Simulation to obtain the associated serum K yielded a right-shifted distribution (median = 4.4 mmol/L; 4.8% below SRI; 10.8% above SRI). Sensitivity for detection in serum (flagged below SRI) for samples originating as hypokalemic in plasma was 45.7% (specificity = 98.3%). Sensitivity for detection in serum (flagged above SRI) for samples originating as hyperkalemic in plasma was 56.6% (specificity = 97.6%). Conclusions: Simulation results indicate that serum K should best be thought of as an inferior substitute marker for plasma K. These results follow simply from the variable component of serum K compared to plasma K. Plasma should be the preferred specimen type for K assessment.

Automated summary

Serum potassium exhibits a positive shift relative to plasma potassium due to clotting, which means that plasma potassium results outside of the reference interval may not produce classification-concordant results in serum. In this study, simulation results indicate that serum potassium should be considered an inferior substitute marker for plasma potassium.