Lessons learned on the path to a healthier brain: dispelling the myths and challenging the hypotheses

Abstract

Neurologic dysfunction remains the most significant complication associated with cardiopulmonary bypass (CPB). The insidious change of cognitive decline has been perceived as a key factor that has contributed to the shift to percutaneous intervention for coronary disease. Current neuropsychologic testing provides the most sensitive means of demonstrating clinically relevant cerebral damage of this nature. Through extensive experience in randomized clinical trials of over 900 patients undergoing CPB, our team has addressed several key hypotheses related to the embolic/ischemic nature of cerebral injury in cardiac surgery, using this testing. In the first temperature study, patients randomized to hypothermia with passive re-warming had a lower incidence of neurocognitive deficit when compared with those patients who were actively re-warmed to 37 degrees. In order to clarify the role of the hypothermia as opposed to the re-warming process, a second temperature study was completed. In the hypothermic group, patients were cooled and maintained at 34 degrees with no active re-warming whereas, in the normothermic group, the patients were kept at 37 degrees throughout the perioperative period. No difference in neurocognitive outcome in the two groups was seen, implying that the benefit seen in the first temperature study was related not to the hypothermia, but rather to the absence of active re-warming. In the cardiotomy study, patients were randomized to either a control group in which their cardiotomy blood was returned unprocessed, or a treatment group in which this blood was sequestered and processed with centrifugal washing and fat filtration. No significant difference in neurocognitive outcome was found in these two groups. On the other hand, there was a significant increase in bleeding and transfusion requirements in the treatment group. Many of our daily practices in CPB management are based upon assumptions from observational studies without sound reference to evidence-based medicine. Our recent studies have challenged our assumptions related to ischemia and embolic events during CPB. They have also confirmed that, when high standards in trial design are applied, the results can have universal implications in terms of our practice.