Pseudohypernatremia and pseudohyponatremia: a linear correction

Serum sodium is commonly measured by direct potentiometry (DNa), in blood gas panels, or indirect potentiometry (INa), in metabolic panels run on chemistry analyzers. Abnormal values of the serum non-water fraction interfere with INa, with low values causing pseudohypernatremia (INa > DNa) and high values causing pseudohyponatremia (INa < DNa). Previous attempts to derive a linear correction for the difference between INa and DNa (ΔNa) arising from non-water bias--using serum total protein (TP) or albumin (ALB) to represent the non-water fraction--have yielded inconsistent results, possibly owing to differences in sample inclusion criteria, analytic platforms and statistical approach.

We quantified the effects of TP and ALB on ΔNa in 774 critical care patients with closely timed metabolic and gas panels, adjusting for other known effects.

ΔNa varied inversely with TP, ALB, and the glucose difference between chemistry and gas panels (ΔGlu), and directly with pH and bicarbonate. The effect of TP on ΔNa was essentially linear, but that of ALB was not; hence, further analysis focused on TP. By multiple linear regression, ΔNa decreased by 0.64 ± 0.06 mEq/L for each 1 g/dL increase in TP, adjusted for ΔGlu, pH, and regression to the mean; the TP effect was slightly steeper (0.69 ± 0.06 mEq/L), when adjusted for bicarbonate instead of pH.

For each 1 g/dL rise or fall in TP, clinicians may find it useful to adjust INa by 0.7 mEq/L in the same direction in order to correct INa for non-water bias.