Effects of clomethiazole on neuropsychological outcome following coronary artery bypass graft surgery

Introduction

The γ-aminobutyric acid A receptor agonist clomethiazole has been shown to have neuroprotective properties in animal models of global and focal brain ischaemia. In the present study we investigated the efficacy of clomethiazole in improving neuropsychological outcome after coronary artery bypass surgery.

Materials and methods

Two hundred and forty-five patients scheduled for coronary artery bypass surgery were prospectively randomized at two centres to intravenous clomethiazole edisilate (8mg/ml) or placebo (0.9% sodium chloride) in a double-blind trial. The drug was infused after induction of anaesthesia and continued until the end of surgery. Coronary artery grafting was completed during mild-to-moderate hypothermia (28–32°C) cardiopulmonary bypass. Baseline neuropsychological assessment was made the day before surgery, using a battery of eight tests, and repeated 4–7 weeks after surgery. Neuropsychological outcome was evaluated by two methods: postoperative change compared with baseline of a global test score, which combined the scores from the eight tests; and the change in individual test scores after surgery compared with baseline.

Results

Neuropsychological assessments were completed in 219 patients (110 clomethiazole and 109 placebo). The mean age in both groups was 64.5 years (range 50-84 years) with a male sex distribution of 89% in the clomethiazole and 76% in the placebo group. There was no difference between the two groups in the change before and after surgery of either the global or individual test scores.

Conclusion

Clomethiazole was not found to influence neuropsychological outcome in patients undergoing coronary artery surgery.

Funding

Astra Arcus AB, Sweden and Astra USA Inc funded the project.