Remote Ischemic Preconditioning for Carotid Endarterectomy

Multiple large, high quality randomized trials have shown carotid endarterectomy (CEA) is effective in decreasing future risk of stroke in patients with carotid artery stenosis. Outcomes after carotid endarterectomy have improved over time. The major risks including stroke and myocardial infarction (MI) are rare (<3% stroke and 4% for MI. However, subtle degrees of cerebral ischemia and myocardial injury are more common. Research is now focused finding ways to reduce these subclinical adverse effects of CEA.

Due to its high metabolic activity, the brain is especially vulnerable to periods of ischemia during carotid cross clamping. Ischemic tolerance has been demonstrated after direct ischemic conditioning in the brain. However, direct conditioning is difficult and potentially dangerous when is comes to carotid interventions making remote ischemic preconditioning an attractive alternative. In animal models, remote ischemic preconditioning (RIPC) has been shown to produce an equivalent response to direct neuronal conditioning at the cellular level.

The precise mechanisms underlying the phenomenon of RIPC have yet to be fully elucidated. However, It is likely that both neural and humoral mechanisms are at play. Multiple studies have shown decreased levels of inflammatory markers in brains of animal models undergoing RIPC and then middle cerebral artery occlusion.

There has only been one study of RIPC in carotid endarterectomy so far. Patients were randomized to 10 min ischemia on each leg prior to clamping the carotid. Primary outcome was significant postoperative deterioration in saccadic latency determined by quantitative oculometry (time taken to respond and fix on a visual stimulus that appears suddenly). Additionally, troponins were drawn up to 48 hours post operatively. There was deterioration in quantitative oculometry in 8/25 RIPC and 16/30 control (p=0.11) and no difference in troponins. However this was a small number of patients.

Major clinical events such as stroke or MI are uncommon following CEA. This hampers the assessment of new, novel interventions as any trial would require several thousand patients to detect a useful clinical effect. The only alternative is to use surrogate end points to obtain "proof of concept" justifying larger trials. Several serum markers of neuronal damage such as S100-beta and neuron-specific enolase have been identified but are not reliable or specific enough to be used clinically. Another surrogate that is directly related to the concept of subtle degrees of neuronal ischemia occurring during CEA is neurocognitive function.