In Reply

We thank Dr. Crystal for his interest in our article entitled “Thoracic Epidural Anesthesia with Ropivacaine Does Not Compromise the Tolerance of Acute Normovolemic Anemia in Pigs,”¹  and we do very much appreciate his comments. In summary, Dr. Crystal addresses two important points: first, the limitation of the whole-body approach applied in our experimental model and, second, the relatively low hemoglobin concentrations at baseline.

Before taking up these comments, we would like to rectify a methodological issue. Dr. Crystal states that whole-body oxygen consumption (Vo₂) was calculated according to Fick equation. Actually, Vo₂ was directly measured using a metabolic monitor. This is an important detail, as in the presence of oxygen supply dependency, the reverse Fick method becomes imprecise resulting in underestimation of Vo₂.²  Of note, the onset of oxygen supply dependency was the indicator of our target parameter Hb_crit.

Our experiments were performed in juvenile pigs. Physiologic hemoglobin values in pigs range from 7 to 8.5 g/dl, and we agree with Dr. Crystal’s objection that this would be considered as severe anemia in men. The comparatively high oxygen-extraction rate (O₂-ER) at baseline indicates that animals were adapted to these hemoglobin levels. Nevertheless, in previous studies as well as in the present study, we still observed increases of O₂-ER compensating for progressive hemodilution.^1,3,4  Inasmuch, data interpretation should rather aim at the evaluation of physiologic mechanisms maintaining tissue oxygenation than at the extrapolation of absolute values to the clinical setting.

Although our study was not designed to investigate anemia tolerance on the organ-specific level, we are aware that this point represents a major limitation. Recently, Lauscher et al.⁵  studied organ-specific anemia tolerance by investigating molecular markers of tissue hypoxia in several organs at different stages of anemia. Consistently with Dr. Crystal’s findings,⁶  renal tissue oxygenation was found impaired, before whole-body Hb_crit was met, as indicated by increased levels of pimonidazole binding and vascular endothelial growth factor. These findings are elucidated by Dr. Crystal’s comments describing the characteristics of renal perfusion and oxygen extraction during acute anemia. Regarding these essential compensatory mechanisms during acute anemia, the kidney differs fundamentally from other organs, indicating that further investigation of renal anemia tolerance might be of particular interest. This is the case because the evidence is amounting that a restrictive transfusion practice is associated with decreased renal morbidity, for example, in patients undergoing cardiac surgery.⁷ 

In our experimental study, the institution of thoracic epidural anesthesia (TEA) resulted in a decrease in vascular resistance and O₂-ER. Particularly in the light of the preexisting anemia, this finding may be interpreted as an indicator of improved tissue perfusion because Vo₂ remained constant after epidural injection of 0.2% ropivacaine. This interpretation, however, raises the question, how TEA might have influenced perfusion pressure and regional blood flow to and within the organs and whether these phenomena might be dose dependent. Although our data cannot answer these questions, we do very much appreciate Dr. Crystal’s considerations on (re)distribution of regional blood leading to the conclusion that this point deserves further research.

We agree that many points need to be clarified before drawing the conclusion that TEA is safe at the lowest acceptable level of acute anemia, and we would like to emphasize that we abstained from drawing such conclusions in our article. What we found out is that, on the whole-body level, essential mechanisms of acute anemia are maintained despite sympathetic block induced by TEA. We would be honored if this finding had provoked interest in further research.