See Article page 214 in the July 2023 issue. Commentary: Red blood cells transfusion in patients undergoing congenital cardiac surgery: Still far from physiology-based practice David Faraoni, MD, PhD, a and James A. DiNardo, MD b Although transfusions can save lives, 1 transfusion of allo- genic blood is not without consequences, 2 especially in pe- diatric cardiac patients where the high incidence of alloimmunization is not inconsequential. 3 Due to a lack of evidence, 4 red blood cell (RBC) transfusions are adminis- tered based on clinical judgments without evidence that ox- ygen consumption (Vo 2 ) has become oxygen delivery (Do 2 )-dependent and potentially limited by hemoglobin concentration. Mubbasheer and colleagues 5 use a modification of the Barnea and colleagues 6 mathematical model of single- ventricle physiology and its underlying assumptions to demonstrate that a hemoglobin level of 9 g/dL would lead to severe arterial (arterial oxygen saturation <70%) and venous (venous oxygen saturation <40%) hypoxemia in the presence of a cardiac index of 6 L/m 2 /min, Vo 2 of 150 mL/min/m 2 , and a Qp/Qs 1. They determine that a cardiac index around 9 L/m 2 /min or a hemoglobin concen- tration 13 g/dL would be needed to maintain optimal levels of Do 2 and Vo 2 . The model is elegant but unfortu- nately systemic and tissue Do 2 is not quite so simple. Blood flow is regulated at 3 places in the circulation: the systemic circulation (cardiac output), the regional circulations (the distribution of blood flow between organs), and the microcirculation (the distribution of blood flow within organs). Although Do 2 can systematically be increased by RBC transfusion, this does not guarantee that Do 2 is increased at the level of the microcirculation. Us- ing a mathematic model describing the treatment of normo- volemic anemia with blood transfusion, Li and colleagues 7 found that the influence of RBC transfusion on Do 2 varies significantly depending on the ability of the endothelium to respond to increases in wall shear stress induced by blood viscosity. In a microvasculature responsive to wall shear stress, RBC transfusion increases nitric oxide production and induces vasodilation, which results in increased Do 2 despite the increase in blood viscosity. In the presence of nonresponsive endothelium, RBC transfusion may lower Do 2 due to an unopposed increase in blood viscosity. Furthermore, a minimum viscosity level is necessary to generate the shear stress and the release of nitric oxide and prostacyclin needed to maximize cardiac output. 8 Simi- larly, Zimmerman and colleagues 9 have suggested that the optimal hematocrit level should be defined as the hemato- crit at which increased oxygen-carrying capacity and oxygen-diffusive losses due to reduced blood flow velocity from increased viscosity are balanced such that Do 2 is maximized. Chronic cyanosis has been shown to be From the a Arthur S. Keat Division of Pediatric Cardiovascular Anesthesia, Depart- ment of Anesthesiology, Perioperative, and Pain Medicine, Texas Children’s Hos- pital, Baylor College of Medicine, Houston, Tex; and b Division of Cardiac Anesthesia, Department of Anesthesiology, Critical Care, and Pain Medicine, Bos- ton Children’s Hospital, Harvard Medical School, Boston, Mass. Disclosures: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest. Received for publication Oct 3, 2022; accepted for publication Oct 22, 2022; available ahead of print Oct 27, 2022. Address for reprints: David Faraoni, MD, PhD, Arthur S. Keat Division of Pediatric Cardiovascular Anesthesia, Department of Anesthesiology, Perioperative, and Pain Medicine, Texas Children’s Hospital, 6651 Main St, Suite 1940.22, Houston, TX 77030 (E-mail: david.faraoni@bcm.edu). J Thorac Cardiovasc Surg 2024;167:e24-6 0022-5223/$36.00 Copyright Ó 2022 by The American Association for Thoracic Surgery https://doi.org/10.1016/j.jtcvs.2022.10.025 Systemic Regional Microcirculation Effect of RBC transfusion on DO2 & VO2 While RBC transfusion remains the treatment of choice to treat acute anemia, a single transfusion threshold is still not a viable approach. Further studies are needed evaluate the effect of RBC transfusion on DO2and VO2at the level of the microcirculation. Optimal Hb CO HR SV CaO2 1.34  Hb SpO2 + 0.003  PaO2  Systemic DO2 1. RBC transfusion increases hemoglobin and DO2 at the level of the systemic circulation 2. Increase in blood viscosity releases NO -> Increase microvascular DO2 3. Concept of optimal hemoglobin to maximize microvascular DO2 4. Stored RBCs manifest slower O2 unloading which may compromise the efficacy of transfusions Hemoglobin g/dL Microviscular DO2 Microvascular DO2 The effect of RBC transfusion on DO 2 and VO 2 . Created with BioRender.com. CENTRAL MESSAGE A single transfusion threshold cannot be recommended. Tools to determine DO 2 and VO 2 at the level of the microcirculations are urgently needed to facilitate physiology-based transfusion therapy. e24 The Journal of Thoracic and Cardiovascular Surgery c February 2024 CONGENITAL: PERIOPERATIVE MANAGEMENT: COMMENTARY CONG