Correspondence  |   June 2015
In Reply
Author Notes
  • University Hospital Frankfurt, Frankfurt/Main, Germany (A.P.).
  • (Accepted for publication February 21, 2015.)
    (Accepted for publication February 21, 2015.)×
Article Information
Correspondence   |   June 2015
In Reply
Anesthesiology 6 2015, Vol.122, 1440-1441. doi:
Anesthesiology 6 2015, Vol.122, 1440-1441. doi:
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 Hbcrit.
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 Hbcrit 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.
Competing Interests
The authors declare no competing interests.
Andreas Pape, M.D., Oliver Habler, M.D., Ph.D. University Hospital Frankfurt, Frankfurt/Main, Germany (A.P.).
Pape, A, Weber, CF, Laout, M, Steche, M, Kutschker, S, Horn, O, Zwissler, B, Habler, O Thoracic epidural anesthesia with ropivacaine does not compromise the tolerance of acute normovolemic anemia in pigs.. Anesthesiology. (2014). 121 765–72 [Article] [PubMed]
Kemming, GI, Meisner, FG, Kleen, M, Habler, OP Calculation is unsuitable for determination of O2-consumption (V. o. 2) in case of O2-supply-dependency.. Eur J Med Res. (2002). 7 139–48 [PubMed]
Pape, A, Kutschker, S, Kertscho, H, Stein, P, Horn, O, Lossen, M, Zwissler, B, Habler, O The choice of the intravenous fluid influences the tolerance of acute normovolemic anemia in anesthetized domestic pigs.. Crit Care. (2012). 16 R69 [Article] [PubMed]
Pape, A, Steche, M, Laout, M, Wedel, M, Schwerdel, F, Weber, CF, Zwissler, B, Habler, O The limit of anemia tolerance during hyperoxic ventilation with pure oxygen in anesthetized domestic pigs.. Eur Surg Res. (2013). 51 156–69 [Article] [PubMed]
Lauscher, P, Kertscho, H, Schmidt, O, Zimmermann, R, Rosenberger, P, Zacharowski, K, Meier, J Determination of organ-specific anemia tolerance.. Crit Care Med. (2013). 41 1037–45 [Article] [PubMed]
Crystal, GJ Regional tolerance to acute normovolemic hemodilution: Evidence that the kidney may be at greatest risk.. J Cardiothorac Vasc Anest. (2015). 29 320–7 [Article]
Gross, I, Seifert, B, Hofmann, A, Spahn, DRPatient blood management in cardiac surgery results in fewer transfusions and better outcome.. Transfusion. (2015). [Epub ahead of print]