Graded interference with the direct potentiometric measurement of sodium by hemoglobin

Sodium concentration is measured by either indirect (I_Na) or direct potentiometry (D_Na), on chemistry and gas panels, respectively. A spurious difference between these methods (ΔNa=I_Na-D_Na) can be confusing to the clinician. For example, variation in serum total protein (TP) is well known to selectively interfere with I_Na. Red cells have been suggested to interfere with D_Na, but both positive and negative interference have been reported. In this study, the effect of gas panel hemoglobin (Hb) on ΔNa was examined.

ΔNa was calculated in 772 pairs of closely-timed chemistry and gas panels (median: 4min. apart), retrospectively collected from our critical care units, with 1 pair per patient. Hb was treated as a categorical or continuous variable and tested for linear and non-linear effects, with adjustment for 3 known influences on ΔNa-TP, bicarbonate (tCO₂), and the chemistry-gas panel glucose difference (ΔGlu).

Hb ranged from 3.5 to 22.0g/dL [35-220g/L]. In categorical analysis, ΔNa increased with Hb, and the effect was essentially linear. By simple regression, ΔNa rose 0.06±0.03[SE]mmol/L per 1g/dL [10g/L] increase in Hb (p<0.05), but confounding was suspected because Hb also correlated (p<10^-3) with TP, tCO₂, and ΔGlu. Using multiple regression to adjust for the confounders, ΔNa rose 0.15±0.03mmol/L per 1g/dL [10g/L] rise in Hb (p<10^-6).

Increasing Hb spuriously decreases D_Na and increases ΔNa. A linear correction for this artifact can reduce the discordance between I_Na and D_Na, promoting their interchangeable use.