Known and Unknown Unknowns in Making Erythrocyte Transfusion Decisions.

Erythrocyte transfusion, used as both a prophylactic and therapeutic intervention, is a cellular transplantation that comes with consequent sequelae including immediate and long-term engraftment of donor leukocytes in the recipient, and other immunologic adversities. It is, therefore, incumbent upon clinicians to identify when erythrocyte transfusion is indicated. This issue of Anesthesiology contains an important publication by Zeroual et al. that investigates the consequence of increasing the restrictiveness of transfusion guidelines. Non–actively bleeding postcardiac surgery patients in the intensive care unit (ICU) in whom hemoglobin concentration fell to less than 9 g/dl were randomly allocated by Zeroual et al. to either standard-of-care erythrocyte transfusion or to an experimental arm in which individuals would be transfused only if their hemoglobin was less than 9 g/dl and their superior vena cava oxyhemoglobin saturation (which does not include contribution from the inferior vena cava, thus distinguishing it from true mixed venous oxyhemoglobin saturation, usually clinically obtained from the pulmonary artery) was less than or equal to 65%. The addition of this criterion for transfusion naturally led to a decreased incidence of erythrocyte transfusion in the ICU (from 100% to 68%), with half of the individuals who were untransfused in the ICU remaining untransfused at hospital discharge; the fraction of patients requiring transfusion from randomization to hospital discharge was also significantly different between the two arms (P = 0.0058). The importance of Zeroual et al.’s work is the implementation of adding a physiologic criterion, to the sole traditional criterion of hemoglobin concentration. It was noted in an earlier article that to understand when oxygen delivery no longer meets oxygen need, an accurate measure of oxygenation at the cellular or tissue level is required, along with an understanding of the physiologic/pathophysiologic consequences of anemia for the critical organ(s) in each individual patient. Two decades later, erythrocyte transfusion decision-making still requires: (1) an ability to define when erythrocyte transfusion is physiologically required; and (2) clear understanding of the relative safety of transfusing erythrocytes versus not (untransfused anemia). Zeroual et al. believe that superior vena cava oxyhemoglobin saturation is a measure that can be used to define erythrocyte need. All surrogates, including superior vena cava oxyhemoglobin saturation are second best to the real measure of interest, must be validated, and should be used only when the latter cannot be assessed. Unfortunately, in this circumstance we have been offered no data to support the notion that at a superior vena cava oxyhemoglobin saturation of less than or equal to 65% oxygen delivery is inadequate: no systemic or individual organ measures of inadequate oxygenation are presented. Decreased venous oxygen content is a consequence of increased tissue oxygen extraction—a normal physiologic response—but not a demonstration that the response mechanisms (increased cardiac output, increased oxygen extraction, or both) are not sufficient to compensate for the lesser hemoglobin concentration. Healthy humans respond to acute severe anemia with increased cardiac output and increased tissue extraction of oxygen as measured by decreased mixed venous (pulmonary artery) oxyhemoglobin saturation (the latter at a hemoglobin concentration of 5 g/dl is a mean of 69.6%), but without