Despite the considerable technological progress made in the last decades in the biomedical field, no measuring system has yet fully succeeded in providing a reliable, accurate, safe and, cost-effective measure of the critical care analytes (CCAs) in the blood to be used for the real-time monitoring of routine extracorporeal (blood) circulation (ECC). In our recent article, we described and demonstrated an innovative measuring instrument that could allow to overcome all current limitations preventing the real-time measurement of the blood-pCO₂ during routine ECC. In this article, we investigate the robustness of such a measuring system to the considerable inter- and intra-variability in blood flow and hematocrit that characterize the ECC treatments. The obtained results demonstrate that, although during the tests the flow and hematocrit values were significantly varied (pCO₂ from ≈ 20 mmHg, to ≈ 110 mmHg; hematocrit from 32%, to 40%; flow from 250 ml/min, to 400 ml/min), the measuring system continued to guarantee a measurement error in the range [-4, 4] mmHg, thus fully complying with the metrological requirements for the in-line and real-time monitoring of blood -pCO₂ during ECC.