Lidocaine for Neuroprotection During Cardiac Surgery

描述(申请人提供)：每年接受心脏手术的老年患者中，手术后认知障碍的发生率很高。术后认知缺陷(POCD)出现在36-50%的患者术后早期，已被证明对术后一年的生活质量有不利影响。尽管在技术、药理学和围手术期器官保护方面的重大进步降低了心脏手术相关的死亡率，但POCD的发生率在过去十年中几乎没有变化。虽然已经提出了多种原因导致这种神经损伤，包括脑栓塞过程和低灌流，但功能障碍的程度很可能受到定义缺血和再灌流的炎症反应的显著调节。我们的多学科神经学结果研究小组(NORG)的目标是了解心脏手术后神经和神经认知功能障碍的潜在机制，并减少这些破坏性后果的发生率。最近，我们在心脏手术期间和术后输注利多卡因，并发现了利多卡因对非糖尿病受试者POCD的保护作用的初步数据。我们认为，静脉注射抗心律失常剂量的利多卡因通过稳定膜和防止初始血管闭塞期间的离子流量，进而改善继发性炎症变化来提供神经保护。因此，我们的前瞻性、随机、双盲介入临床试验的主要目的是确定利多卡因在减少术后认知功能衰退方面的有效性。其次，我们将通过测量颈动脉单核细胞、多形核细胞和血小板激活梯度来确定利多卡因对整个脑血管炎症反应的影响。对病人或病人家人来说，没有什么比成功的手术延长生命但降低生活质量更具破坏性的了。没有什么比患者神经认知状态恶化导致的独立性丧失更有可能对生活质量产生不利影响了。由于仍有大量患者在接受心脏手术，一种简单而廉价的干预措施，如静脉注射利多卡因，有可能极大地提高世界各地数十万患者的生活质量。公共卫生相关性：认知障碍是心脏手术的常见并发症。在这项研究方案中，我们计划使用利多卡因，一种廉价且常见的药物，以减少术后认知功能障碍。利多卡因疗法的使用为改善认知功能带来了巨大的希望，因此，我们越来越多的老年患者的生活质量和功能独立性得到了改善。

DESCRIPTION (provided by applicant): Cognitive impairment after surgery occurs frequently in the large number of increasingly elderly patients undergoing cardiac surgery every year. Postoperative cognitive deficit (POCD) is present in 36-50% of patients in the early phases after surgery and has been shown to adversely impact quality of life as much as one year after surgery. Despite substantial advancement in technology, pharmacology, and perioperative organ protection leading to reductions in mortality associated with cardiac surgery, the incidence of POCD has changed little over the last ten years. While multiple etiologic factors have been proposed for this neurological injury including cerebral embolic processes and hypoperfusion, it is likely that the degree of dysfunction is significantly modulated by the inflammatory responses that define ischemia and reperfusion. The objective of our multidisciplinary Neurological Outcome Research Group (NORG) is to understand the mechanisms underlying neurologic and neurocognitive dysfunction after cardiac surgery and to reduce the incidence of these devastating outcomes. Recently we administered lidocaine as an infusion during and after cardiac surgery and found preliminary data for a protective effect of lidocaine against POCD in non-diabetic subjects. We believe that intravenous lidocaine at antiarrhythmic doses offers neuroprotection by membrane stabilization and prevention of ion flux during initial vessel occlusion, followed by amelioration of the secondary inflammatory changes. Thus the primary aim of our prospective, randomized, double-blind interventional clinical trial is to determine the effectiveness of lidocaine in reducing postoperative cognitive decline. Secondarily, we will determine the effect of lidocaine upon the inflammatory response across the cerebral vasculature by measuring the jugular-arterial monocyte, polymorphonuclear, and platelet activation gradients. Little is more devastating to a patient or the patient's family than to have a successful operation that prolongs life but diminishes the quality of that life. Nothing is more likely to adversely impact quality of life than deterioration in a patient's neurocognitive status with resultant loss of independence. With the large number of patients still undergoing cardiac surgery, a simple and inexpensive intervention such as intravenous lidocaine holds the potential of dramatically increasing the quality of life for hundreds of thousands of patients world- wide. PUBLIC HEALTH RELEVANCE: Cognitive impairment is a common complication of cardiac surgery. In this research proposal, we plan to use lidocaine, an inexpensive and commonly available drug, to reduce postoperative cognitive dysfunction. The use of lidocaine therapy holds great promise for improving cognitive function and as a consequence, quality of life and functional independence for the large number of our increasingly elderly patients.