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

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.