Anesth Analg 2000;91:244-245
© 2000 International Anesthesia Research Society
LETTERS TO THE EDITOR
Is Tranexamic Acid Indicated for Total Knee Replacement Surgery?
Keyvan Karkouti, MD, FRCPC, MSc
Director, Perioperative Blood Conservation Program oronto General Hospital, University Health Network Toronto, Ontario, Canada
Dr. Zohar et al. (1), compared the blood-sparing effects of tranexamic acid (TA) and acute normovolemic hemodilution (ANH) in patients undergoing total knee replacement (TKR). There are at least two reasons why this comparison is inappropriate.
First, as the authors state, TKR is performed with an occlusive tourniquet and is associated with minimal intraoperative but extensive postoperative blood loss. For this very reason, ANH as performed in this study (i.e., re-infusion of blood on arrival in the postanesthesia care unit) is not expected to be very beneficial for TKR and is therefore not recommended (2).
Second, the study design was such that the ANH group was put at an increased risk of receiving blood. There are two reasons for this: the preoperative hematocrit was smaller in the ANH group (even if it was not statistically significant), and more importantly, patients in the ANH group were much more likely to reach the transfusion trigger of 27% as a result of hemodilution (they received 22 mL/kg more fluid and had urine outputs similar to the TA group). This increased risk of transfusion is evident by the extremely frequent transfusion rate in the ANH group (65% vs 5% in the TA group), despite only a modest difference in postoperative blood loss between the two groups. In fact, the expected transfusion rate for this procedure in patients lacking autologous blood is less than 30% (3). At our institution, the current transfusion rate is less than 15%.
The role of TA in TKR can only be assessed by randomized, placebo-controlled clinical trials. Few such studies have been published to date (4–6). Because TA is an expensive treatment modality with potentially serious adverse effects, further trials are required before its use can be recommended. Furthermore, because TA is not yet considered to be standard-practice for TKR, I do not agree with the authors’ statement that such trials are now ethically unacceptable.
References
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Zohar E, Fredman B, Ellis M, et al. A comparative study of the postoperative allogeneic blood-sparing effect of tranexamic acid versus acute normovolemic hemodilution after total knee replacement. Anesth Analg 1999;89:1382–7.[Abstract/Free Full Text]
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National Heart Lung and Blood Institute Panel on the use of autologous blood. Transfusion alert: use of autologous blood. Transfusion 1995;35:703–11.
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Cushner FD, Scott WN. Evolution of blood transfusion management for a busy knee practice. Orthopedics 1999;22 (suppl):s145–7.[Medline]
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Benoni G, Fredin H. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: a prospective, randomised, double-blind study of 86 patients. J Bone Joint Surg Br 1996;78:434–40.
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Benoni G, Lethagen S, Fredin H. The effect of tranexamic acid on local and plasma fibrinolysis during total knee arthroplasty. Thromb Res 1997;85:195–206.[Web of Science][Medline]
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Hiippala ST, Strid LJ, Wennerstrand MI, et al. Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty. Anesth Analg 1997;84:839–44.[Abstract]
Response
Edna Zohar, MD,
Brian Fredman, MB, BCh,
Martin Ellis, MB, BCh, and
Robert Jedeikin, MBChB, FFA(SA)
Department of Anesthesiology and Critical Care Meir Hospital Kfar Sava, Israel
We disagree with Dr. Karkouti’s comment that, when performed for total knee replacement (TKR), hemodilution is not expected to be an effective blood-sparing strategy. Because TKR is associated with extensive postoperative blood loss (which is not controlled by surgical techniques), transfusing blood that is rich in platelets and clotting factors has the theoretical potential to decrease postoperative bleeding and allogeneic blood requirements. Furthermore, when compared with control, normovolemic hemodilution (NVHD) has been shown to significantly reduce allogeneic blood transfusion after TKR (1,2). Similarly, after TKR, tranexamic acid administration significantly reduces allogeneic blood transfusion (3). Because both blood conservation strategies may be associated with unwanted adverse effects, we believe that a comparative study designed to assess the relative efficacy of these two strategies is not only appropriate but essential before evidence-based decisions can be made.
Dr. Karkouti suggests that, because NVHD reduces patient hematocrit, our study design increased the likelihood that the NVHD study group would receive allogeneic blood. However, the decrease in hematocrit is not study-design dependent. By definition, acute hemodilution is associated with a decreased hematocrit. Therefore, it would be impossible to compare the relative efficacy of NVHD versus any other blood-sparing protocol without accepting this inherent limitation. Furthermore, despite the hemodilution-induced decrease in hematocrit, when compared with control, NVHD significantly reduced the allogeneic blood requirement after TKR (1).
Because the frequency of postoperative transfusion is influenced by an institution-specific "transfusion culture," predetermined "transfusion trigger," as well as other patient and doctor variables, expected transfusion rates can be meaningful only if they are the result of vigorously controlled, randomized, prospective studies. Unfortunately, Dr. Karkouti presents "soft" data to support the claim that the hemodilution-induced reduction in perioperative hematocrit resulted in the "extremely frequent" transfusion rate (65%) among our NVHD treatment group. Neither the citation that the "expected transfusion rate for this procedure [TKR] in patients lacking autologous blood is less than 30%" (4), nor the fact that at Dr. Karkouti’s institution, "the current transfusion rate is less than 15%" fulfill the criteria required to facilitate meaningful interpretation. In contrast, in a prospective, randomized study, Olsfanger et al. (1), administered allogeneic blood to 100% of the control patients. Furthermore, in a similarly designed study, Hiippala et al. (3), administered allogeneic blood to 90% of the control patients. Thus, it is incorrect to suggest that NVHD increases the likelihood of allogeneic blood transfusion after TKR. Finally, these transfusion statistics support our comment that "randomizing patients into a treatment group that would most probably be exposed to more allogeneic blood requirements (and blood-induced complications) was ethically unacceptable."
References
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Olsfanger D, Fredman B, Goldstein B, et al. Acute normovolaemic haemodilution decreases postoperative allogeneic blood transfusion after total knee replacement. Br J Anaesth 1997;79:317–21.[Abstract/Free Full Text]
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Schmied H, Schiferer A, Sessler DI, Meznik C. The effect of red-cell scavenging, hemodilution, and active warming on allogenic blood requirements in patients undergoing hip or knee arthroplasty. Anesth Analg 1998;86:387–91.[Abstract]
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Hiippala S, Strid LJ, Wennerstrand MI, et al. Tranexamic acid radically decreases blood loss and transfusions associated with total knee replacement. Anesth Analg 1997;84:839–44.
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Cushner FD, Scott WN. Evolution of blood transfusion management for a busy knee practice. Orthopedics 1999;22 (suppl):s145–7.
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