Bleeding complications after off-pump coronary artery bypass surgery: Interpreting the contribution of hetastarch

To the Editor:

I read with interest the article by Hecht-Dolnik and colleagues1 examining the association between intraoperative administration of hetastarch and bleeding complications after off-pump coronary artery bypass graft surgery. The authors conclude that administration of 1 L of hetastarch in addition to albumin and crystalloid versus albumin and crystalloid alone resulted in increased risk of postoperative transfusion requirement and chest tube drainage. Given the existing body of evidence showing an association between greater quantitative blood loss with the use of high molecular weight (HMW) hetastarch compared with both lower molecular weight hetastarch and albumin, in both cardiac2, 3 and noncardiac surgery,4, 5 it is not clear what further information this study provides. Also, features of the study design and ambiguity within the manuscript itself both create difficulty for a reader hoping to interpret the validity or clinical significance of these findings.

First, the composition of hetastarch solution used in the study was never specified. Choice of commercially available hetastarch solutions in the United States at the time this study took place was limited to HMW, highly substituted starches composed in either saline or balanced salt solution. The differing behavior of hetastarch solutions related to their molecular weight, degree of substitution, and electrolyte composition has been a topic of frequent investigation and commentary.6, 7, 8, 9, 10, 11 Unfortunately, failure of Hecht-Dolnik and colleagues to better identify the hetastarch used does not allow us to fully interpret their results.

Second, the reason for greater blood loss and transfusion requirement is not entirely clear. Standardized (protocol or goal-directed) fluid administration was not described in the methods and presumably was not used during the conduct of the study, nor does it appear that the anesthesiologists administering fluids during the case were blinded to subject randomization. Not surprisingly, the overall volume of colloid was significantly greater in patients in the hetastarch versus albumin group. This greater overall colloid administration may have expanded plasma volume sufficiently to cause subsequently greater clotting factor dilution, decreased blood viscosity, and increased venous return and cardiac output. In turn, these circulatory effects alone may explain the increased chest tube drainage and transfusion requirement seen in the hetastarch group, irrespective of any specific influence hetastarch may or may not have had on platelet aggregation or coagulation.12

Although transfusion requirement certainly constitutes one clinically important end point, some equally compelling secondary outcomes, including length of ventilation, intensive care unit stay and hospitalization, rate of return to the operating room, and survival to hospital discharge, did not differ significantly. It would have been interesting to know whether thromboelastogram measurements showed correlation with subsequent transfusion requirement. Beyond that, the opportunity was not taken to explore other physiologic consequences reasonably attributable to fluid management. For example, effective plasma volume expansion with any colloid, particularly hetastarch, may improve microvascular perfusion and tissue oxygenation, even at the cost of greater quantitative blood loss.12, 13, 14, 15 Therefore, a tradeoff between approaches may exist. Although the chosen sample size may not have been sufficient to find a difference between measures indicative of tissue oxygenation, their omission is nevertheless unfortunate. The clinical importance of plausibly relevant end points such as infection, wound healing, organ function, cognition, overall cost of care, and longer-term mortality would have justified their inclusion as secondary outcome variables.

Ultimately, clinical interventions must be made with a balanced understanding and consideration of their possible benefit and harm. The recent availability of lower molecular weight hetastarch solutions in the United States, which exhibit lesser dose-dependent coagulation impairment and platelet inhibition, may eventually lead to shift in practice away from HMW hetastarch solutions altogether. There will undoubtedly be more post-marketing studies comparing these newer hetastarch solutions to HMW hetastarch and albumin. Unfortunately, Hecht-Dolnik and colleagues1 studied only those end points that are easily predicted and measured. I sincerely hope that future investigative efforts will encompass a more comprehensive set of clinically meaningful end points, so that dollars and effort spent on research will yield novel, informative data that will be helpful in guiding clinical decision-making.