Emergency transfusion for acute severe anemia: a calculated risk.

An editorial about a case report is unusual, but no more so than the case reported by Dai et al. in this issue of the journal. They report survival, without apparent sequelae, of a 53-year-old man with a hemoglobin concentration as low as 0.7 g/dL (hematocrit 2.2%) for several hours. Despite the presence of a low fibrinogen concentration and an elevated partial thromboplastin time (not discussed here), successful management was facilitated by surgical control and minimal intraoperative blood loss. The reported nadir hemoglobin concentration may be the lowest known during acute anemia associated with survival, the previous apparently being 1.1 g/dL reported by Zollinger et al. This raises 2 important questions: (1) How is this possible? and (2) What alternatives are possible when crossmatched erythrocytes are not available? It is not possible to know accurately the hemoglobin concentration that is associated with mortality or serious morbidity, because prospective experiments in humans with those end points are impossible and data from laboratory animals cannot be extrapolated to humans because of potentially important differences among species. Retrospective analyses of hospital databases and case reports regarding mortality associated with severe acute anemia have suggested that the median value is 5 g/dL. In a recent reexamination of those data, it was estimated that the median hemoglobin concentration associated with anemia-induced mortality is approximately 2.5 g/dL (R. B. Weiskopf, unpublished data, 2010). Cardiovascular disease increases that value (also R. B. Weiskopf, unpublished data, 2010). Retrospective examination of other databases relating preoperative hemoglobin concentration to postoperative mortality does not provide useful information because they do not separate those not transfused, nor are they able to account for the rationale for lack of transfusion or provide the hemoglobin concentration at death. Adequately powered prospective randomized clinical trials in adults and children in intensive care units have not found different mortality rates between those transfused with “restrictive” or “liberal” strategies that resulted in hemoglobin concentrations of approximately 8.5 and 10.5 g/dL. Considering that the human mean fatal hemoglobin concentration is approximately 2.5 g/dL, and that this case report documents a hemoglobin concentration that is lower than previously known during acute anemia, it may seem difficult to understand survival. Nevertheless, there are data to assist in the explanation of this seemingly exceedingly improbable event. The patient’s fraction of inspired oxygen (Fio2) was nearly 1.0 throughout the 12 hours of surgery. Similarly, in the case reported by Zollinger et al., Fio2 was 1.0 and Pao2 400 mm Hg at the time of the nadir hemoglobin concentration. Classic thought is that the amount of oxygen dissolved in plasma (the solubility of oxygen in plasma is 0.0031 mL/dL/mm Hg O2) is too little to be of physiologic consequence. Whereas that may be so during ordinary circumstances with an Fio2 of 0.21, dissolved oxygen can be of substantial benefit during severe anemia, when the Fio2 and Pao2 are high. Hyperoxia reduces mortality of pigs subjected to acute severe anemia and maintained at their critical hemoglobin concentration. In healthy humans, breathing oxygen reverses the neurocognitive deficits and increased P300 latency (the neurophysiologic correlate) induced by severe anemia. High Pao2 in healthy humans decreases the heart rate response to acute severe anemia (also J. Feiner, et al., unpublished data, 2010), and oxygen supplementation decreases heart rate after abdominal surgery. The physiologic effect of a Pao2 in excess of 400 mm Hg has been estimated to be equivalent to approximately 3 g/dL hemoglobin (also J. Feiner, et al., unpublished data, 2010). Thus, the physiologic effect of breathing oxygen when added to the patient’s native hemoglobin of 0.7 g/dL produced a heart rate equivalent to nearly 4 g/dL hemoglobin, a value associated with approximately 80% survival (R. B. Weiskopf, unpublished data, 2010). Provision of a high Fio2 can be a useful “bridge” until red cells are available for transfusion. As important as the above information may be, it is perhaps more important to know the hemoglobin concentration that is associated with significant morbidity than that associated with mortality, because clinicians would prefer to prevent the former before it results in the latter. The brain seems to be more sensitive to acute anemia than is the heart (R. B. Weiskopf, unpublished data, 2010). Healthy humans have degraded neurocognitive function From the University of California, San Francisco, San Francisco, California (Professor Emeritus).