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The effect of storage time of human red cells on intestinal microcirculatory oxygenation in a rat isovolemic exchange modelRaat NJ, Verhoeven AJ, Mik EG, et al. Crit Care Med 2005; 33: 39-45.Reviewer: Michael H. Wall, MD
Abstract: Raat et al1 evaluated the ability of stored human blood to provide tissue oxygenation to the intestinal microcirculation in a rat model of severe isovolemic anemia. Human red blood cells (RBC's) were leuko depleted, washed (to eliminate rat-human transfusion reactions), suspended in buffer (containing adenine glucose and mannitol and stored at 6°C for 2-6 days, 2-3 weeks or 5-6 weeks). Levels of 2-3 DPG were almost un-measurable in the blood stored for 2-3 or 5-6 weeks (0.3 and .08 µmol/gHb) vs. stored 2-6 days (8.1 µmol/gHb). ATP levels were significantly decreased only in blood stored 5-6 weeks (3.7 vs. 3.5 vs. 2.4 µmol/gHb at 2-6 d, 2-3 wks and 5-6 wks). The animals were anesthetized and isovolemically hemodiluted to severe anemia (Hb = 4.6 g/dL). Then they underwent exchange transfusion with stored blood (2-6 d, 2-3 wks or 5-6 wks) while keeping the Hb constant. Finally, the animals were transfused to a Hb of 10 g/dL with stored blood. There were no differences or changes in pH, PaO2, PaCO2 or base excess at any time in any group. Mean arterial pressure was significantly lower and intestinal blood flow was significantly higher after hemodilution in all groups and these changes persisted throughout the experiment. Intestinal oxygen delivery (DO2int) was significantly lower than baseline following hemodilution and following exchange transfusion in all 3 groups. Following transfusion to a Hb of 10 gm/dL DO2int returned to baseline in all three groups. Intestinal microvascular PO2 (µPO2) was significantly lower than baseline following hemodilution and exchange transfusion. Exchange transfusion with blood stored for 5-6 weeks decreased µPO2 by 28%. There was no change in µPO2 during exchange transfusion with blood stored 2-3 d or 2-3 wks. When the animals were transfused from a Hb of 4 to 10 gm/dL µPO2 increased by 28-32% in all groups, but remained significantly below baseline. Finally, there were no differences in RBC deformability evaluated by ectacytometry between blood stored 2-6 d, 2-3 wks or 5-6 wks. The authors conclude that during exchange transfusion at very low Hb tissue oxygen delivery is impaired with RBC's stored for 5-6 weeks, but not with blood stored 2-3 wks or 2-6 days. Further, the impaired delivery is not due to low levels of 2-3 DPG or impaired RBC deformability. Comments: Recently, several studies have shown associations between "older blood" (i.e. stored longer) and decreased tissue oxygenation, increased infections, increased oxygen failures and increased mortality.2 One possible explanation for these associations has been that older blood is not able to oxygenate tissues, however very few studies have actually evaluated tissue oxygenation. This well designed study showed that in an organ with relatively low oxygen consumption, at extreme degrees of anemia, human RBC's stored up to 2-3 weeks can oxygenate tissue even without 2-3 DPG. And blood as old as 5-6 weeks can increase tissue oxygenation when the Hb is increased from 4 to 10 gm/dL. This is reassuring since approximately 1/3 of all blood transfused has been stored for >3 weeks. Like all good studies, several new questions have emerged and many remain unanswered - What happens to tissues with higher oxygen demands (heart, kidney, brain)? What happens to tissue oxygenation with transfusion in diseased or injured tissues (trauma, burns, sepsis)? If the fall in tissue oxygenation seen during extreme anemia is not due to decreased 2-3 DPG or impaired deformability, what was it due to? Future investigations examining the mechanisms causing decreased µPO2 following exchange transfusion with stored blood and studies of tissue oxygenation in other organ beds need to be done. References
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