Cerebral protection by lignocaine during heart surgery : Evidence from neuropsychological test performance

Abstract

Cognitive deficits following heart surgery have been reliably demonstrated and, over the past decade, the search for mechanisms to protect against such impairment has accelerated. The present study investigates the possible neuroprotective effect of the drug lignocaine, a class a 1 anti-arrhythmic agent that directly interferes with the depolarisation of the cell membrane by blocking the influx of sodium into the cells. The study was a double blind, randomised trial. Elective valve surgery patients were given either lignocaine (n=27) or placebo (saline) (n=28) intravenous infusions during their operations according to a standard protocol. Patients were administered a battery of neuropsychological tests prior to and at 10 days, l0 weeks and six months following their surgery. The degree of cognitive impairment/improvement was determined using accepted criteria. The results suggest that lignocaine conferred a persistent protective effect. Group mean percentage change scores over the four test sessions demonstrated that lignocaine treated patients significantly improved on all tests, except the Rey Figure copy (ceiling effect). By contrast, the placebo group demonstrated significant improvement in some tests and no improvement in others. In all cases the magnitude of improvement was greater for the lignocaine group, which culminated in a mean improvement of 22.2% for lignocaine patients, and 10.6% for saline patients at six months. Furthermore, the results also suggested that patients who were more vulnerable preoperatively gained the most benefit from lignocaine treatment. In addition, self-report data which examined memory performance in activities of daily living showed that lignocaine patients had better daily postoperative memory performance, a result that was corroborated by observations from their partners. Analysis of individual test results also demonstrated an advantage for the lignocaine patients, who demonstrated significant improvements in a greater number of tests, suggesting that lignocaine not only conferred an advantage in the magnitude of performance but also in broader cognitive domains. The data suggest that postoperatively both lignocaine and control groups improved in terms of attention, concentration, conceptual tracking, psychomotor speed, and the executive functions of planning, organisation, complex motor responses, visuo-spatial organisation, and self monitoring. Verbal learning and memory also improved. However, lignocaine patients seemed to show improvement in an additional cluster of executive functions; complex conceptual tracking, complex scanning and sequencing, and flexible planning ability, and the improvement in learning and memory tasks was greater. There was a suggestion that lignocaine treatment also assisted with encoding and retention of verbal and non-verbal information. Preoperative, perioperative (notably microemboli count), or postoperative variables could not explain the superior neuropsychological test performance by lignocaine patients and neither practice effects nor emotional factors (depression and anxiety) account for these improvements. It is suggested that improvements in both patient groups are most likely due to improved cerebral perfusion associated with surgical treatment of the patients' heart disease, and that the additional protection afforded by lignocaine arises from its capacity to minimise the non-specific negative effects of cardiopulmonary bypass surgery.