Vascular Determinants of Anesthesia-Induced Hypotension at the Extremes of Age

极端年龄时麻醉引起的低血压的血管决定因素

• 批准号: 10711597
• 负责人: Emmett E Whitaker
• 金额: --
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2023-09-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10711597
• 关键词: Address; Adolescent; Adult; Age; Age Years; Anesthesia procedures; Anesthetics; Biomechanics; Blood Pressure; Blood Vessels; Cerebrovascular Circulation; Data; Development; Elderly; Ensure; Equilibrium; Exposure to; Foundations; Frequencies; General Anesthesia; General anesthetic drugs; Goals; Health Care Costs; Homeostasis; Hypotension; Impairment; In Vitro; Individual; Infant; Injury; Lead; Mesenteric Arteries; Morbidity - disease rate; Norepinephrine; Operative Surgical Procedures; Organ; Patient Care; Patients; Perfusion; Perioperative Care; Population; Property; Public Health; Publishing; Rattus; Regimen; Research; Risk; Role; aged; cerebral artery; constriction; experience; hemodynamics; hypoperfusion; improved; in vivo; insight; middle cerebral artery; mortality; neonate; optimal treatments; preservation; prevent; programs; treatment strategy; young adult

PROJECT SUMMARY/ABSTRACT Each year, hundreds of millions of patients are exposed to general anesthesia for surgery. Millions of these patients are particularly vulnerable to injury during surgery because they are either very young (e.g., neonates and infants) or older (>70 years of age). One critical role of the anesthesiologist is to ensure hemodynamic stability and adequate organ perfusion (e.g., prevent intraoperative hypotension). When caring for patients at the extremes of age, this can be challenging because up to 80% of neonates, infants, and older adults experience intraoperative hypotension. This represents a significant public health problem as intraoperative hypotension has been shown to cause significant morbidity and mortality in this population and is associated with millions of dollars in additional healthcare costs per year. Though it is clear that intraoperative hypotension is a significant problem in neonates, infants, and older adults, the mechanisms that underlie the increased risk of intraoperative hypotension and its consequences remain unclear. To address this, we propose to use complementary in vitro and in vivo approaches to provide new insights into mechanisms by which patients at extremes of age suffer intraoperative hypotension with increased frequency. The goal of this research program is to investigate how the unique properties of the vasculature at the extremes of age contribute to the development of intraoperative hypotension in the setting of commonly used general anesthetics. Our published and preliminary data show that mesenteric arteries in juvenile rats are stiffer with diminished capacity to constrict to norepinephrine compared to adults. In contrast, middle cerebral arteries from juvenile rats demonstrated reduced stiffness and impaired autoregulation of cerebral blood flow when compared to adults. Taken together, these data provide the foundation upon which we hypothesize that the underlying mechanism of increased risk of intraoperative hypotension in patients at the extremes of age is vascular in origin. Over the next 5 years, we propose to investigate vascular mechanisms by which patients at the extremes of age are at increased risk of intraoperative hypotension and resultant organ hypoperfusion when exposed to general anesthesia. By studying isolated mesenteric and cerebral arteries we will identify biomechanical and cellular mechanisms that differentiate the very young and older adults from adults of intermediate age. Separately, we will use in vivo approaches to identify definitions of hypotension that are determined based upon organ perfusion. Finally, we will determine which anesthetic regimens are least likely to produce hypotension, and which therapies used to treat hypotension best balance improving blood pressure while preserving whole- body organ perfusion. These distinct but complementary lines of inquiry will be an important step towards optimizing perioperative care for those at the extremes of age.

项目摘要/摘要 每年，数亿例患者暴露于全身麻醉以进行手术。数百万 这些患者在手术过程中特别容易受伤，因为他们要么很小（例如， 新生儿和婴儿）或年龄较大（> 70岁）。麻醉师的一个关键作用是确保 血液动力学稳定性和足够的器官灌注（例如，预防术中低血压）。照顾时 年龄极端的患者可能具有挑战性，因为多达80％的新生儿，婴儿和老年人 体验术中低血压。这代表了术中重大的公共卫生问题 性低血压已被证明会引起该人群的显着发病率和死亡率，并且与 每年有数百万美元的额外医疗保健费用。虽然很明显术中 低血压是新生儿，婴儿和老年人的重要问题，是基于的机制 术中低血压及其后果的风险增加尚不清楚。 为了解决这个问题，我们建议使用互补的体外和体内方法来提供新的见解 进入极端的机制，术中患者术中低血压随着增加 频率。该研究计划的目的是研究脉管系统的独特特性 在常用的情况下，年龄的极端有助于术中低血压的发展 一般麻醉药。我们发表的初步数据表明，少年大鼠中的肠系膜动脉很僵硬 与成年人相比，对去甲肾上腺素收缩的能力降低。相比之下，大脑中部动脉 从少年大鼠中表现出较低的刚度和脑血流自动调节的降低 与成人相比。综上所述，这些数据为我们假设的基础提供了基础 在极端的患者术中低血压风险增加的潜在机制 是血管起源。 在接下来的5年中，我们建议研究极端患者的血管机制 年龄的术中低血压和导致器官灌注的风险增加 全身麻醉。通过研究孤立的肠系膜和脑动脉，我们将确定生物力学和 细胞机制将非常年轻和老年人与中级成年人区分开。 另外，我们将使用体内方法来确定基于 器官灌注。最后，我们将确定哪种麻醉方案最不可能产生低血压， 以及哪种疗法用于治疗低血压最佳平衡，以改善血压，同时保存全部 身体器官灌注。这些独特但互补的询问路线将是迈向的重要一步 为极端年龄的人优化围手术期护理。