Lidocaine for Neuroprotection During Cardiac Surgery

利多卡因在心脏手术期间的神经保护作用

• 批准号: 7698221
• 负责人: Joseph P Mathew
• 金额: $ 35.86万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-20 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7698221
• 关键词: Age; Atherosclerosis; Attenuated; Biological Preservation; Blood specimen; Cardiac; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cerebrum; Chemotactic Factors; Clinical Trials; Clinical Trials Design; Cognitive deficits; Complication; Data; Deterioration; Dose; Double-Blind Method; Effectiveness; Endothelial Cells; Event; Family; Functional disorder; Genes; Genetic Polymorphism; Goals; Hematocrit procedure; Hemodilution; Hour; Impaired cognition; Impairment; Incidence; Inflammatory; Inflammatory Response; Infusion procedures; Intervention; Intravenous; Investigation; Ions; Ischemia; Leukocytes; Lidocaine; Life; Measures; Membrane; Nervous System Trauma; Neurocognitive; Neurologic; Neurological outcome; Operative Surgical Procedures; Organ; Outcome; Outcomes Research; Patients; Perioperative; Pharmaceutical Preparations; Pharmacology; Phase; Placebos; Platelet Activation; Population; Postoperative Period; Prevention; Process; Quality of life; Randomized; Reperfusion Therapy; Research; Research Proposals; Risk Factors; Safety; Stroke; System; Technology; Testing; Therapeutic Agents; Therapeutic Embolization; base; cell injury; cognitive function; experience; health care delivery; improved; monocyte; mortality; multidisciplinary; neuroprotection; non-diabetic; older patient; prospective; protective effect; public health relevance; randomized placebo controlled trial; success

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.

描述（申请人提供）：手术后的认知障碍经常发生在每年接受心脏手术的日益老年患者中。术后认知缺陷（POCD）在手术后的早期患者中存在于36-50％的患者中，并且已被证明会在手术后一年内对生活质量产生不利影响。尽管技术，药理学和围手术器官保护的大幅进步导致与心脏手术相关的死亡率降低，但在过去的十年中，POCD的发生率几乎没有改变。尽管已经提出了有关这种神经系统损伤的多种病因因素，包括脑栓塞过程和灌注不足，但定义缺血和再灌注的炎症反应可能会显着调节功能障碍的程度。我们的多学科神经系统结果研究小组（NORG）的目的是了解心脏手术后神经系统和神经认知功能障碍的机制，并减少这些毁灭性结果的发生。最近，我们在心脏手术期间和之后施用了利多卡因作为输液，并找到了利多卡因在非糖尿病患者中对POCD的保护作用的初步数据。我们认为，抗心律失常剂量的静脉内利多卡因可通过膜稳定和预防在初始血管闭塞期间通过膜稳定和预防离子通量进行神经保护作用，然后改善二次炎症性变化。因此，我们前瞻性，随机，双盲介入的临床试验的主要目的是确定利多卡因在降低术后认知下降方面的有效性。其次，我们将通过测量颈颈单核细胞，多形核和血小板激活梯度来确定利多卡因对脑脉管系统炎症反应的影响。对患者或患者的家人来说，几乎没有什么比成功延长寿命但降低生活质量的成功手术更具毁灭性的。没有什么比在患者的神经认知状况恶化的情况下更可能对生活质量产生不利影响的可能性。随着大量患者仍在接受心脏外科手术，诸如静脉内利多卡因等简单且廉价的干预措施具有显着提高世界上数十万患者的生活质量的潜力。公共卫生相关性：认知障碍是心脏手术的常见并发症。在这项研究建议中，我们计划使用利多卡因（一种便宜且常用的药物）来减少术后认知功能障碍。利多卡因治疗的使用具有改善认知功能的巨大希望，因此，我们日益老年患者的使用质量，生活质量和功能独立性。