Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

低温停循环期间体温的认知影响

• 批准号: 9312866
• 负责人: G. Chad Hughes
• 金额: $ 68.74万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9312866
• 关键词: Adult; Adverse effects; Affect; Agitation; Aorta; Blood Circulation; Body Temperature; Brain; Brain Injuries; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cerebrum; Cognition; Cognitive; Complication; Confusion; Coupled; Data; Delirium; Dependence; Family; Functional disorder; Goals; Heart; Human; Impaired cognition; Incidence; Inflammation; Inflammatory; Interruption; Ischemia; Lead; Leukocytes; Life; Light; Magnetic Resonance Spectroscopy; Measures; Metabolic; Modernization; Morbidity - disease rate; Neurocognitive; Neurologic; Neurologic Dysfunctions; Neurological outcome; Neurons; Observational Study; Operative Surgical Procedures; Organ; Outcome; Outcomes Research; Pathway interactions; Patients; Pattern; Perfusion; Postoperative Period; Quality of life; Randomized; Randomized Clinical Trials; Research Proposals; Resistance; Retrospective Studies; Role; Safety; Temperature; Testing; Therapeutic Intervention; Ubiquitin; Vascular blood supply; aortic arch; base; biological adaptation to stress; functional loss; improved; inflammatory modulation; multidisciplinary; natural hypothermia; new therapeutic target; novel therapeutic intervention; operation; patient safety; prospective; protective effect; randomized trial; risk minimization; sobriety; standard of care

The use of deep hypothermia (<20°C) for cerebral protection ushered in the modern era of safe and effective operations on the heart and aorta. In large part due to advanced circulatory management strategies, surgical procedures on the proximal aorta and arch utilizing deep hypothermic circulatory arrest have steadily increased over the last decade. Despite these advances, neurologic complications remain a sobering limitation. Indeed, 7%-13% of patients endure permanent neurologic dysfunction. In addition, postoperative cognitive decline (POCD) occurs in 36% of cardiac surgery patients at 6 weeks after surgery, and importantly, persists in 42% of patients up to 5 years after surgery and reduces quality of life. Although deep hypothermia has been the standard of care for decades in adult patients requiring circulatory arrest, moderate hypothermia is now more commonly used in many centers. However, this transition to moderate temperatures has been based entirely on observational studies that have not adequately assessed neurological or neurocognitive outcomes. Little is more devastating to a patient or the patient's family than to have a successful operation that prolongs life, but is complicated by cognitive impairment resulting in a diminished quality of life and loss of functional in- dependence. The long-term goal of our multidisciplinary Neurologic Outcome Research Group is to understand the mechanisms underlying neurologic and neurocognitive dysfunction after cardiac surgery, and to reduce the incidence of these devastating outcomes. In the proposed study, we will test our hypothesis that deep hypo- thermia (<20°C) during surgical circulatory arrest limits POCD and preserves brain connectivity to a greater degree than moderate hypothermia (24.1°C-28°C) and that low hypothermia (20.1°C-24°C) is non-inferior to deep hypothermia. Thus the primary aims of our prospective, randomized clinical trial are to 1) determine the effect of deep vs low vs moderate hypothermia on neurocognitive function and quality of life after surgical cir- culatory arrest; 2) determine the effect of deep vs low vs moderate hypothermia on brain connectivity and met- abolic signatures of neuronal damage following surgical circulatory arrest; and 3) determine how temperature management affects leukocyte SUMOylation patterns as a mechanism of inflammatory modulation in surgeries employing circulatory arrest. Our proposed study will be the first randomized trial to evaluate the effects of deep vs low vs moderate hypothermia during circulatory arrest on neurocognitive function and functional brain connectivity. Our preliminary data strongly supports a detrimental effect of moderate hypothermia during circu- latory arrest and thus this study is likely to dramatically alter practice and improve patient safety. This study will also be the first study in humans to assess the role of the small ubiquitin-like modifier conjugation pathway in protecting the brain during cardiac surgery requiring circulatory arrest. Thus, this study is significant, and will vertically advance the field of cardiac surgery by revolutionizing our understanding of the effects of hypother- mia on neurologic and neurocognitive outcomes, by providing strong evidence for optimal hypothermic tem- peratures during surgical circulatory arrest, and by identifying new targets for therapeutic intervention to in- crease the resistance of organs to a transient interruption in blood supply.

深低温(&lt；20°C)脑保护的使用开启了安全有效的现代时代 心脏和大动脉的手术。在很大程度上是由于先进的循环管理策略，外科手术 使用深低温停循环的近端主动脉和弓部手术稳步增加。 在过去的十年里。尽管取得了这些进展，但神经系统并发症仍然是一个令人警醒的限制。的确， 7%-13%的患者患有永久性神经功能障碍。此外，术后认知能力下降 (POCD)发生在36%的心脏手术患者术后6周，重要的是，持续在42% 患者术后长达5年，并降低了生活质量。尽管深低温一直是 几十年来的标准护理需要循环骤停的成年患者，现在更多的是中度低温 在许多中心普遍使用。然而，这种向中等温度的转变完全是基于 关于没有充分评估神经或神经认知结果的观察性研究。 对患者或患者家人来说，没有什么比成功的手术延长时间更具破坏性了 生活，但复杂的认知障碍，导致生活质量下降和功能丧失- 依赖。我们多学科神经学成果研究小组的长期目标是了解 心脏手术后神经和神经认知功能障碍的潜在机制，并减少 这些毁灭性后果的发生率。在这项拟议的研究中，我们将检验我们的假设，即深度次生- 外科停循环期间的体温(&lt；20°C)限制了POCD并保护了大脑与更大的 比中低温(24.1°C-28°C)和低低温(20.1°C-24°C)的程度不低于 深度低温症。因此，我们的前瞻性随机临床试验的主要目的是：1)确定 深低温与低低温与中低温对术后神经认知功能及生活质量的影响 计算停滞；2)确定深低温与低低温与中低温对脑连通性和MET的影响。 手术循环停止后神经元损伤的代谢特征；以及3)温度如何决定 手术中作为炎症调节机制的处理影响白细胞苏木糖化模式 使用循环停搏。我们建议的研究将是第一个评估药物疗效的随机试验 深低温与低低温与中低温停循环对神经认知功能和脑功能的影响 连通性。我们的初步数据有力地支持了在以下情况下亚低温的有害影响 因此，这项研究很可能会极大地改变实践，提高患者的安全性。这项研究将 也是第一个在人类中评估小泛素样修饰物结合途径在 在需要停循环的心脏手术中保护大脑。因此，这项研究具有重要意义，并将 通过彻底改变我们对降温效应的理解，垂直推进心脏外科领域- MIA对神经学和神经认知结果的影响，通过为最佳低温温度提供强有力的证据- 外科停循环期间的体温变化，以及确定治疗干预的新靶点。 提高器官对血液供应短暂中断的抵抗力。