Accuracy of the strong-ion gap: Dependency on albumin electrical charge and fluid electroneutrality

Figge's pH-dependent approximation for albumin's electrical charge for native albumin has been widely used in acid-base analysis since 1992. Fogh-Andersen (FA) subsequently demonstrated that albumin binds ions, primarily Cl^-, increasing its net negative charge. A pH-dependent equation for ion-bound albumin was derived and compared with the Figge formulation for calculating the strong ion gap (SIG) using the electroneutrality relationship. Model performance was evaluated using datasets from studies of normal blood, where SIG is expected to be near zero. The primary dataset from Krbec et al. included over 300 measurement sets on blood from healthy subjects exposed to wide variations in PCO₂, with comprehensive electrolyte and acid-base measurements. Across multiple data sets, FA model SIG values were consistently closer to zero than those using the Figge model. Analyses of three additional normal datasets supported this finding, whereas results from one study lacking Mg²⁺ measurements were less conclusive. In one of three clinical data sets, both formulations predicted SIG estimates that were clinically significant. The FA formulation appears preferable in the normal data sets studied, but further validation is needed before broad clinical replacement of the Figge formulation is warranted.