Improving interpretation of metabolic acid–base disorders by correcting pH-dependent bias in base excess partitioning

Background: Base excess (BE) partitioning is an established tool for bedside interpretation of metabolic acid-base disorders. However, this method assumes that changes in plasma strong ion difference, estimated as [Na+]-[Cl-], directly relate to changes in standard BE. This assumption holds in isolated plasma but fails in vivo, where pH-dependent redistribution between body compartments alters plasma strong ion difference without producing an equivalent change in standard BE. We hypothesised that this introduces a clinically relevant pH-dependent bias into BE partitioning and that adjusting the [Na+]-[Cl-] reference value for pH would correct it. Methods: Unmeasured ions were quantified using conventional BE partitioning and a novel pH-corrected version, in which the [Na+]-[Cl-] reference was adjusted by +1.5 mEq L-1 for every -0.1 change in pH. Agreement with strong ion gap was assessed in 5976 ICU patients from AmsterdamUMCdb using Bland-Altman analyses (including pH-stratified subgroups) and linear regression to quantify the independent effect of pH. Results: The conventional method demonstrated wide limits of agreement (-5.6 to 2.9 mEq L-1) and a strong confounding effect of pH (1.45 mEq L-1 per 0.1 pH unit). The pH-corrected algorithm markedly improved agreement with the strong ion gap (limits of agreement -4.4 to 0.4 mEq L-1) and substantially reduced the confounding effect of pH (0.15 mEq L-1 per 0.1 pH unit). Conclusions: Conventional base excess partitioning is subject to a clinically relevant pH-dependent error. A variable, pH-adjusted [Na+]-[Cl-] reference value eliminates this error and provides a more reliable assessment of metabolic acid-base disturbances, especially in patients with severe acidaemia or alkalaemia.