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Ann Thorac Surg 2003;75:1683
© 2003 The Society of Thoracic Surgeons
a Hygeia Associates, 17988 Brewer Rd, Grass Valley, CA 95949, USA
e-mail: mwilkes{at}hygeiaassociates.com
To the Editor:
It has often been argued that the molecular weight of hydroxyethyl starch (HES) is a key determinant of coagulopathy. For that reason we stratified the results of our meta-analysis by molecular weight and found the difference in postoperative bleeding between albumin and high molecular weight HES (450 kDa) to be similar to that between albumin and medium molecular weight HES (200 kDa) [1]. It is correct to note that the pooled difference in bleeding for medium molecular weight HES was of borderline significance (p = 0.058), although absence of significance in such a subgroup analysis is not unexpected because of diminution in statistical power. In addition to the randomized trials included in our meta-analysis, there have been two randomized trials of patients undergoing cardiopulmonary bypass that directly compare HES preparations of differing molecular weights, namely, 120 kDa versus 400 kDa HES [2] and 130 kDa versus 200 kDa HES [3]. In neither trial was there a significant difference in postoperative blood loss. In a nonrandomized, controlled trial [4] of 200 consecutive patients, mean postoperative mediastinal blood loss among patients receiving 200 kDa HES was 834 ± 499 mL compared with 640 ± 388 mL for albumin recipients (p = 0.002). Thus, evidence currently is lacking to support the hypothesis that HES molecular weight differences exert an important impact on bleeding after cardiac surgical procedures.
Based on a study of 5,426 patients [5], there is evidence that in routine cardiac surgery practice, postoperative bleeding volumes are not normally distributed but rather exhibit rightward skewing. However, this observation should not be extrapolated to randomized trials with highly select, low-risk patient populations like those included in our meta-analysis. For distributions such as bleeding volumes with a lower boundary of zero, rightward skewing is indicated when the standard deviation substantially exceeds one half of the mean value. The pooled blood loss for adult patients receiving albumin in our meta-analysis was 693 ± 350 mL compared with 789 ± 487 mL for the HES group. Thus, our data are consistent with a normal distribution.
Bélisle and Hardy [5] reported excessive mediastinal drainage (>1,000 mL) in 29% of patients but did not describe the fluid management regimens used. We estimated excessive bleeding in 19% of adult albumin recipients versus 33% of patients receiving HES. In the absence of information about fluids administered in the study by Bélisle and Hardy [5], no precise judgment can be made regarding the compatibility of our data with theirs.
My coauthors and I [1] acknowledged in our report that the difference in mean bleeding is not necessarily of clinical importance. For that reason we estimated the percentages of patients with excessive bleeding that might prompt clinical intervention, for example, blood product administration, delay of extubation, or reexploration for bleeding.
Hydroxyethyl starch decreases factor VIII and von Willebrand factor levels more than can be explained by hemodilution alone, induces thrombocytopenia, impairs platelet function, enhances fibrinolysis, and prolongs prothrombin time and activated partial thromboplastin time, and patients undergoing a cardiac surgical procedure may be particularly susceptible to such effects [6]. Our meta-analysis of randomized trials together with extensive evidence from nonrandomized trials indicates that bleeding after cardiopulmonary bypass operations is increased with the use of HES compared with albumin.
References
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