Quantifying pH-induced changes in plasma strong ion difference during experimental acidosis: clinical implications for base excess interpretation

It is commonly assumed that changes in plasma strong ion difference (SID) result in equal changes in whole-blood base excess (BE). However, at varying pH, albumin ionic-binding and transerythrocyte shifts alter the SID of plasma without affecting that of whole-blood (SIDwb), i.e., the BE. We hypothesize that, during acidosis, 1) an expected plasma SID (SIDexp) reflecting electrolytes redistribution can be predicted from albumin and hemoglobin's charges, and 2) only deviations in SID from SIDexp reflect changes in SIDwb, and therefore, BE. We equilibrated whole-blood of 18 healthy subjects (albumin=4.8±0.2 g/dL, hemoglobin=14.2±0.9 g/dL), 18 hypoalbuminemic and anemic septic patients (albumin=3.1±0.5 g/dL, hemoglobin=10.4±0.8 g/dL), and 10 healthy subjects after in-vitro induced isolated anemia (albumin=5.0±0.2 g/dL, hemoglobin=7.0±0.9 g/dL) with varying CO2 concentrations (2-20%). Plasma SID increased by 12.7±2.1, 9.3±1.7, and 7.8±1.6 mEq/L, respectively (p<0.01) and its agreement (bias[limits of agreement]) with SIDexp was strong: 0.5[-1.9;2.8], 0.9[-0.9;2.6], and 0.3[-1.4;2.1] mEq/L, respectively. Separately, we added 7.5 or 15 mEq/L of lactic or hydrochloric acid to whole-blood of 10 healthy subjects obtaining BE of -6.6±1.7, -13.4±2.2, -6.8±1.8, and -13.6±2.1 mEq/L, respectively. The agreement between ∆BE and ∆SID was weak (2.6[-1.1;6.3] mEq/L), worsening with varying CO2 (2-20%): 6.3[-2.7;15.2] mEq/L. Conversely, ∆SIDwb (the deviation of SID from SIDexp) agreed strongly with ∆BE at both constant and varying CO2: -0.1[-2.0;1.7], and -0.5[-2.4;1.5] mEq/L, respectively. We conclude that BE reflects only changes in plasma SID that are not expected from electrolytes redistribution, the latter being predictable from albumin and hemoglobin's charges.