Inadequate oxygen delivery during cardiopulmonary bypass drives inflammatory reaction after cardiac surgery

Objectives Systemic inflammatory response syndrome (SIRS) is a common complication following cardiopulmonary bypass (CPB), associated with increased mortality. We assessed the relationship between indexed oxygen delivery (DO2i) during CPB and SIRS. Methods We conducted a prospective observational study at two institutions. The primary endpoint was clinically-defined SIRS 12 hours after surgery. The secondary endpoint was a composite outcome comprising death, TIA/stroke, renal replacement therapy, bleeding, mechanical circulatory support, or ICU stay >96 hours. The primary analysis modeled DO2i in multivariable logistic regression. Linearity was assessed with restricted cubic splines, knot-sensitivity, quintiles, and piecewise fits. The optimal ROC-derived threshold was explored. Patients above and below the threshold were matched 1:1 by propensity score. Structural equation modeling (SEM) assessed mediation between DO2i, SIRS, and outcomes. Results Of 1,154 patients screened, 908 were analyzed; 221 (24.3%) developed SIRS. Median DO2i was lower in the SIRS group (274 vs 302 mL/min/m2, p < 0.001). DO2i was inversely associated with SIRS (aOR 0.798; 95% CI 0.750-0.850, p < 0.001, per +10 mL/min/m2). In the secondary analysis, DO2i ≤ 293 mL/min/m2 was identified as threshold (sensitivity 62%, specificity 74%). Propensity score matched 390 patient pairs, with higher SIRS incidence in the low-DO2i group (33.3% vs 14.4%; p < 0.001). The composite outcome occurred more frequently in the low-DO2i cohort (17.7% vs 8.2%; p < 0.001). SEM showed mediation by SIRS, accounting for 46.2% of the DO2i effect on outcomes (OR 1.052; 95%CI 1.036-1.067; p < 0.001). Conclusion Low DO2i during CPB predicts SIRS and adverse outcomes. Goal-directed perfusion to reduce inflammation warrants evaluation in randomized trials.