Quantifying the effects of hemoglobin saturation on plasma strong ion difference during blood oxygenation and decarboxylation

Abstract The strong ion difference (SID) is assessed to interpret acid–base disorders, yet measured plasma values are influenced by electrolyte redistribution across compartments. Current models focus on pH‐dependent plasma‐erythrocyte shifts. Here, we aim to quantify the effects of hemoglobin oxygen saturation (sO 2 ). We induced oxygenation and decarboxylation of human venous blood ( n = 20) via room‐air equilibration. We modeled the contribution of ∆sO 2 to plasma‐erythrocyte shifts through the Haldane effect and hypothesized that combining sO 2 ‐ with pH‐dependent mechanisms would allow accurate prediction of redistribution related ∆SID. After room‐air equilibration, sO 2 fraction increased by 0.46 [0.39–0.54], CO 2 tension decreased by 29 [25–32] mmHg, and pH increased by 0.25 [0.19–0.32]. SID decreased by 5.3 [4.2 to 5.6] mEq/L, and its changes were independently associated with ∆sO 2 (∆SID/∆sO 2 = −3.0 [−5.4 to −0.67] mEq/L, p < 0.01). Accordingly, when only pH‐dependent redistribution was considered, ∆SID prediction yielded a ∆sO 2 ‐dependent ( p < 0.01) underestimation of measured ∆SID (mean bias [limits of agreement]: −1.6 [−3.7 to 0.5] mEq/L). Including sO 2 ‐dependent effects improved the bias (−0.4 [−2.0 to 1.3] mEq/L) and removed its ∆sO 2 ‐dependence ( p = 0.63), and this result was maintained using a simplified model (∆SID = 1.5·[Hemoglobin+Albumin] g/dL ·∆pH+[Hemoglobin/4] g/dL ·∆sO 2 ). We conclude that ∆sO 2 independently affects ∆SID during blood oxygenation and decarboxylation. Incorporating sO 2 ‐ alongside pH‐dependent electrolyte shifts enables accurate prediction of redistribution‐related ∆SID.