Purine Nucleosides as an Indicator of Cerebral Ischaemia in Local and General Anaesthetic Carotid Endarterectomy

Abstract

Introduction: Neurological events, though rare, are a potential cause of significant morbidity in carotid endarterectomy (CEA). Shunting protects against ischaemic brain injury but is not without inherent risk to patients. In periods of cerebral ischaemia adenosine triphosphate (ATP) is metabolised, leading to accumulation of purine nucleosides. Purine measurements with an amperometric biosensor in patients undergoing CEA with loco-regional anaesthetic have shown a significant rise in purines on carotid cross clamping and subsequent returns to baseline on unclamping. This has proven the ability of this biosensor to allow real time measurements of purine nucleosides in vivo as a marker of developing cerebral ischaemia. The aim of this study was to determine the changes in purine concentrations intraoperatively in patients undergoing GA CEA Methods: CEA was performed in 18 Patients with Local anaesthetic (LA) and 40 patients under general anaesthetic (GA) at two teaching hospitals. 18 patients undergoing inguinal hernia repair were recruited as controls. Purines were measured from radial artery catheter samples at set time points throughout the procedure and recovery up to 24 hours post-operatively. Physiolgical parameters were measured peri-operatively. A selective shunt-patch policy was employed. The GA cohort were analysed in shunted and unshunted subgroups. Results: Physiological parameters between all groups were comparable although The LA cohort had a higher pulse during the clamped phase of CEA.. In the LA cohort there was a 2.8-fold increase in purines during the clamp phase (Median 2.4-6.7 mM). In the GA Cohorts there were no significant increases in purine concentrations on clamping (p=>0.05). There was also no significant difference in purine concentrations between shunted and unshunted GA subgroups during CEA (p=>0.05). The observed difference between GA and LA cohorts on application of the cross clamp was significant (P=0.004). The control cohort demonstrated no significant change in purines at any point. There were no perioperative or medium term neurological complications. Conclusion: These results demonstrate a significant rise in purines in the LA cohort during the clamp phase of CEA. This was not replicated in the GA cohort. This supports existing evidence that cerebral metabolic demand is higher during LA CEA than GA CEA. GA causes a significant decrease in cerebral metabolic rate and loss of metabolic rate-blood flow coupling that may result in “luxury perfusion” of cerebral tissue and subsequently little ischaemic nucleoside production intraoperatively. Previous studies have demonstrated rises in purines under GA with central venous sampling. Purines are inherently unstable in plasma and catabolism and/or reuptake may occur prior peripheral arterial sampling. Analysis of central venous samples may give greater sensitivity to changes in purines during GA CEA. Purines offer real time analysis of evolving brain ischaemia and as such, may aid surgeons with intraoperative decision making around shunting.