Response to Letter Regarding Article, “Continuous-Flow Cell Saver Reduces Cognitive Decline in Elderly Patients After Coronary Bypass Surgery”
Thank you for this opportunity to reply to the comments by Rubens et al with respect to our recent publication.1 Rubens et al imply that we analyzed our cognitive data incorrectly. It appears that they have misinterpreted our intentions with respect to the reference by Rasmussen et al2 that was provided as an example of z score calculation and not for quantifying cognitive decline. Furthermore, we would like to clarify that van Dijk et al3 described the use of z scores as a continuous variable for comparison between the 2 groups and not a decrease of 1 SD in the test Z score in 20% of the tests. As a courtesy to Rubens et al, we have performed an additional analysis using the composite Z scores as a continuous variable. The mean difference in composite z scores was 1.39 versus 0.49 (95% confidence interval 0.13 to 1.67, P=0.021) in the cell saver and control groups, respectively. The results are no different with respect to the primary outcome from our original statistical approach.
Rubens et al emphasize that their definition of postoperative cognitive dysfunction (POCD) was chosen a priori. To our knowledge, all randomized prospective trials use an a priori definition of their primary outcomes and our trial was no different in this respect. We deliberately did not use the so-called “20/20” definition because of the reported high false-positive rates.4
We would also like to point out some of the fundamental differences between our trial1 and the one from Rubens et al5 in an attempt to elucidate why we may have obtained different results. First, the study by Rubens et al5 had 2 different primary outcomes, the proportion of patients requiring red blood cell transfusions as well as the incidence of POCD at 5 days after surgery, whereas our study had only POCD as a primary outcome. In the study from Rubens et al,5 the study power calculations, the cell saver utilization strategy, and the management of blood transfusion were under strict protocol geared toward the transfusion outcome. Neurocognitive function measurements appear to have been regarded as more of a secondary outcome. This methodological approach ignores a potential relationship between the blood product transfusion and cognitive outcome.
Second, we used 2 different cell saver systems with uniquely diverse processing capabilities6 and 2 different approaches to blood management. In our study, we used the continuous-flow cell saver (Fresenius Corporation, Concord, Calif), whereas Rubens et al5 used the intermittent-flow cell saver (BRAT, COBE Cardiovascular Inc). The continuous-flow cell saver may have been more efficient at removing particulate material6 and inflammatory mediators. In our study, the cell saver was used only intraoperatively during the full heparinization, whereas Rubens et al5 used the cell saver up to 4 hours postoperatively when thrombi and microthrombi are more likely to occur. In addition, we did not transfuse any mediastinal drainage blood in the postoperative period, whereas Rubens et al5 transfused shed mediastinal blood in both groups of patients up to 4 hours after surgery. For all of these reasons, we do not think that combining our data would be a valid approach to answer the question of cell saver usage and POCD.
Lastly, we would like to emphasize that, similar to Rubens et al5 we reported a significantly higher usage of fresh frozen plasma in the cell saver group. Yet, these findings did not negate the beneficial effects of continuous cell saver technology in reducing POCD after coronary revascularization surgery. However, we agree with Rubens et al that readers of Circulation should weigh the risk of fresh frozen plasma transfusion versus POCD when interpreting our results.
Djaiani G, Fedorko L, Borger MA, Green R, Carroll J, Marcon M, Karski J. Continuous-flow cell saver reduces cognitive decline in elderly patients after coronary bypass surgery. Circulation. 2007; 116: 1888–1895.
Van Dijk D, Jansen EW, Hijman R, Nierich AP, Diephuis JC, Moons KG, Lahpor JR, Borst C, Keizer AM, Nathoe HM, Grobbee DE, De Jaegere PP, Kalkman CJ. Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. JAMA. 2002; 287: 1405–1412.
Rubens FD, Boodhwani M, Mesana T, Wozny D, Wells G, Nathan HJ. The cardiotomy trial: a randomized, double-blind study to assess the effect of processing of shed blood during cardiopulmonary bypass on transfusion and neurocognitive function. Circulation. 2007; 116 (suppl): I-89–I-97.