The Neuropsychologic Deterioration Seen in the Placebo Group May Have Been a Result of Rigorous Exclusion Criteria: In Reply

To the Editor:—In “Clinical Trial of the Neuroprotectant Clomethiazole in Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial,” by Kong et al., the authors assessed neuropsychologic deterioration following bypass surgery with cardiopulmonary bypass. They are to be congratulated for the rigorous design of their experiment and their willingness to report a “negative” result. Their topic is so important to our patients that model articles such as this, no matter what the result, are of the utmost significance. The authors monitored embolic load during surgery using Doppler ultrasound of the common carotid or middle cerebral artery. Using this measure, they found no difference between the embolic loads in the study and the control groups, nor, as noted, was the neuropsychologic outcome different between the groups. The authors comment, however, that, “the [neuropsychological] deterioration seen in the placebo group was less than anticipated at the planning stage. This may have been a result of the rigorous exclusion criteria. As a result, the study may have been underpowered.” In other words, both groups had an equivalent and better than expected outcome. If embolic load during coronary surgery using cardiopulmonary bypass is related to surgical technique, then this unexpectedly good outcome may be related to the presence of Doppler ultrasound monitoring. At least one article has suggested that surgeons, in the presence of a device that monitors emboli, improve their technique in an effort to avoid creating these emboli. I would say that this explanation is at least as compelling as the idea that the study was underpowered and that Clomethiazole actually is protective.