Significance: Red blood cell transfusions (RBCTs) to restore hemoglobin concentration and hematocrit values in anemic patients are debated in critical illness.

This study presents a novel, non-invasive hybrid diffuse optical monitoring approach for critically ill patients receiving red blood cell transfusions. This technique enables continuous, real-time assessment of microvascular blood oxygenation, oxygen metabolic rate, and blood flow—parameters that are typically inaccessible in this population.

We demonstrate the first application of this method to characterize and quantify physiological responses to transfusion therapy in both cerebral and peripheral tissues. By elucidating the effects of transfusion, which remain debated in critically injured patients, our findings enhance understanding of its systemic impact. The feasibility demonstrated here supports the future development of individualized transfusion strategies aimed at minimizing complications such as hypoxia and ischemia and ultimately improving clinical outcomes.

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