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

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 (sO₂). We induced oxygenation and decarboxylation of human venous blood (n = 20) via room-air equilibration. We modeled the contribution of ∆sO₂ to plasma-erythrocyte shifts through the Haldane effect and hypothesized that combining sO₂- with pH-dependent mechanisms would allow accurate prediction of redistribution related ∆SID. After room-air equilibration, sO₂ fraction increased by 0.46 [0.39-0.54], CO₂ 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 ∆sO₂ (∆SID/∆sO₂ = -3.0 [-5.4 to -0.67] mEq/L, p < 0.01). Accordingly, when only pH-dependent redistribution was considered, ∆SID prediction yielded a ∆sO₂-dependent (p < 0.01) underestimation of measured ∆SID (mean bias [limits of agreement]: -1.6 [-3.7 to 0.5] mEq/L). Including sO₂-dependent effects improved the bias (-0.4 [-2.0 to 1.3] mEq/L) and removed its ∆sO₂-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·∆sO₂). We conclude that ∆sO₂ independently affects ∆SID during blood oxygenation and decarboxylation. Incorporating sO₂- alongside pH-dependent electrolyte shifts enables accurate prediction of redistribution-related ∆SID.