To determine whether colloid choice within the cardiopulmonary bypass (CPB) priming strategy independently modifies the perioperative acid-base trajectory.

Preplanned analysis of a single-center, double-blind, 3-arm randomized controlled trial.

A tertiary academic teaching hospital.

Thirty-four adult patients undergoing elective coronary artery bypass grafting with CPB.

Patients were randomized 1:1:1 to 3 priming strategies (total 1500 mL): albumin-based, gelofusine-based, and retrograde autologous priming (reference group).

Acid–base status was characterized using Stewart’s physicochemical approach at 5 perioperative time points (postinduction to 24 hours post–intensive care unit admission). A linear mixed model was used to assess the effects of priming strategy, time, and additional crystalloids. Across 170 observations, initiation of CPB induced substantial metabolic acidosis (−0.1 pH, −4.3 mmol/L standard base excess, −6.6 mEq/L effective strong ion difference), driven by reductions in apparent strong ion difference and persisting at 24 hours. pH, standard base excess, and effective strong ion difference did not differ among the priming strategies. Albumin attenuated weak acid-anion dilution (+0.79 mEq/L; p = 0.037), while gelofusine increased the strong ion gap (+2.19 mEq/L; p < 0.001). Each additional liter of crystalloid independently lowered pH (−0.011; p = 0.035), standard base excess (−0.99 mmol/L; p = 0.022), and effective strong ion difference (−1.03 mEq/L; p = 0.025), driven by a rise in strong ion gap (+1.24 mEq/L; p = 0.001).

CPB-induced metabolic acidosis is driven predominantly by reductions in apparent strong ion difference and sustained by unbalanced crystalloid load rather than by colloid choice. Acid–base optimization should prioritize balanced, strong ion difference–guided priming fluid and crystalloid strategies over colloid selection.