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.