An equilibrium model was developed to understand interrelated, physicochemical mechanisms leading to blood pH and electrolyte distribution changes in patients because of venovenous extracorporeal membrane oxygenation (ECMO) and carbon dioxide removal. The model consists of plasma and red cell compartments between which water and small ions can move to establish an equilibrium state. Governing forces are as follows: 1) ionic electroneutrality in each compartment; 2) osmotic equilibrium between compartments; 3) mass balance of small ions other than bicarbonate; 4) oxygen (O₂)-dependent hemoglobin (Hb)-Cl binding in red cells; 5) albumin binding to Cl⁻, Ca²⁺, and Mg²⁺ in plasma; and 6) chemical equilibria of carbonates and phosphates in each compartment.

The model was constructed and validated using recent clinical ECMO inlet and exit blood-pH and electrolyte concentration data. The model closely described pH and electrolyte concentration changes in both states, which validated the model.

The model was then used to predict CO₂ and O₂ saturation–induced changes in pH and electrolyte concentrations. It was found that O₂-dependent Hb-Cl binding had a much lesser effect on blood acid–base status changes and electrolyte shifts during ECMO than previously thought.

The model showed that the Cl-shift and Gibbs-Donnan equilibrium effects, characterized by pH and electrolyte distribution changes during ECMO, were primarily caused by changes in pH-induced electrical charge on mainly Hb and other constrained ions in red cells. These insights can improve understanding of the same factors acting when blood traverses the lung.