PeriOperative Interventional Neuroprotection Trial-POINT

围手术期介入神经保护试验点

• 批准号: 6824042
• 负责人: Mark Franklin Newman
• 金额: $ 57.2万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6824042
• 关键词: aging; chemoprevention; clinical research; clinical trials; cognition disorders; coronary bypass; diet therapy; human subject; human therapy evaluation; magnesium; magnesium deficiency; neuroprotectants; neuropsychological tests; nutrition related tag; patient oriented research; postoperative complications; postoperative state

DESCRIPTION (provided by investigator): Cognitive impairment occurs frequently after surgery in the approximately 400,000 patients who undergo cardiac operations each year. An increasing number of these patients are elderly, and we have found that this patient population is particularly susceptible to cognitive dysfunction after cardiac surgery. Cognitive impairment is most notable in the early phases after cardiac surgery, but persistence occurs in an important percentage of patients. While adjectives such as "subtle," "transient," and "subclinical" have been used due to the apparent transient nature of decline, we have identified that perioperative decline is associated with five year cognitive deterioration and reduced quality of life. Multiple strategies, both clinical and pharmacological, have been proposed to reduce the central nervous system dysfunction associated with cardiac surgery. However, most have been unsuccessful, met with very limited success, or are unrealistic from a cost or risk-benefit ratio to be applied to the majority of patients. We will test the ability of supplemental magnesium, achieving plasma levels 2x normal, to provide protection from neurocognitive decline in patients undergoing cardiac surgery. This clinical trial will enroll 400 patients over approximately 48 months. A battery of neurocognitive tests as well as a neurologic assessment will be completed at baseline, discharge, 4 - 6 weeks, and one year postoperatively. Our multidisciplinary research team has extensive experience in assessing neurocognitive decline both short and long-term after cardiac surgery, will allow this project to be accomplished expeditiously both as a pilot clinical and following efficacy trial. Multiple animal studies demonstrate a benefit of magnesium in focal and global models of ischemia. Although still early in enrollment, the Interventional magnesium stroke study (IMAGES) has yielded promising results. Little is more devastating to a patient, the patient's family or those caring for a patient than to have a successful operation that prolongs life, but diminishes the quality of that prolonged life. Nothing is more likely to adversely impact the quality of life than deterioration in a patient?s mental status, particularly those higher faculties that we call cognition. Therefore, we will also determine if magnesium bolus plus infusion given perioperatively can improve quality of life through improved cognitive performance. We propose that magnesium, through one of a number of potential mechanisms will allow us to alter susceptibility to neurocognitive dysfunction and thereby prevent this tragic consequence in the aging population.

描述（由研究者提供）：认知障碍经常发生 大约 400,000 名接受心脏手术的患者在手术后 每年的运营。越来越多的患者是老年人，并且 我们发现这个患者群体特别容易受到 心脏手术后认知功能障碍。认知障碍最为严重 在心脏手术后的早期阶段值得注意，但持续发生在 患者的重要比例。虽然诸如“微妙”之类的形容词 由于明显的瞬态，因此使用了“瞬态”和“亚临床” 衰退的性质，我们已经确定围手术期衰退与 五年内认知能力下降，生活质量下降。多种的 已经提出了临床和药理学策略来减少 与心脏手术相关的中枢神经系统功能障碍。然而， 大多数都没有成功，取得的成功非常有限，或者不切实际 根据适用于大多数患者的成本或风险收益比。我们 将测试补充镁的能力，达到血浆水平 2 倍 正常，以防止患者神经认知能力下降 正在接受心脏手术。该临床试验将招募超过400名患者 大约48个月。一系列神经认知测试以及 神经系统评估将在基线、出院、4 - 6 周时完成， 以及术后一年。我们的多学科研究团队拥有广泛的 评估术后短期和长期神经认知衰退的经验 心脏手术，将使该项目能够迅速完成 作为试点临床和后续疗效试验。多项动物研究 证明镁在局灶性和整体缺血模型中的益处。 尽管介入性镁中风研究仍处于早期阶段 （图片）已经取得了有希望的结果。对一个人来说，没有什么比这更具破坏性了 患者、患者家属或护理患者的人比拥有 成功的手术可以延长生命，但会降低生命质量 延长寿命。没有什么比这更可能对生活质量产生不利影响了 而非患者精神状态的恶化，尤其是那些精神状态较高的患者 我们称之为认知的能力。因此，我们还将确定是否 围手术期给予镁丸加输注可改善生活质量 通过改善认知表现。我们建议镁通过一种 许多潜在机制将使我们能够改变对 神经认知功能障碍，从而防止这种悲惨后果 人口老龄化。