Vasoactive Agents and Cerebral Outcomes in Brain Injury

血管活性药物和脑损伤中的脑结果

• 批准号: 9029235
• 负责人: Monica S Vavilala
• 金额: $ 24.99万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9029235
• 关键词: 4 year old; Adolescent; Affect; Age; Blood Pressure; Brain; Brain Injuries; Brain Ischemia; Caring; Cause of Death; Cerebral perfusion pressure; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrum; Cessation of life; Characteristics; Child; Childhood Injury; Data; Dopamine; Emergency Medicine; Endothelin-1; Epinephrine; Family suidae; Histopathology; Homeostasis; Hypotension; Impairment; Intravenous; Learning; Liquid substance; Measures; Modeling; Newborn Infant; Norepinephrine; Outcome; Patients; Perfusion; Phenylephrine; Physicians; Play; Potassium Channel; Process; Recommendation; Research; Research Personnel; Role; Surgeon; Testing; Trauma; Traumatic Brain Injury; Vasodilation; Vasodilator Agents; Work; adrenomedullin; age related; blood product; boys; disability; evidence based guidelines; fluid percussion injury; girls; hemodynamics; indexing; injured; male; middle cerebral artery; neurovascular unit; pediatric trauma; pediatric traumatic brain injury; prevent; public health relevance; sex; vasoactive agent

 DESCRIPTION (provided by applicant): Trauma is the leading killer of children and adolescents, and traumatic brain injury (TBI) is the leading cause of pediatric trauma related death, where boys and young children have worse outcomes. When caring for injured children, front line physicians such as surgeons, anesthesiologists, emergency medicine physicians, and intensivists often struggle to prevent and/or expediently correct the unwanted but prevalent hypotension. This is problematic because systemic hypotension causes low cerebral perfusion (cerebral perfusion pressure [CPP] and cerebral blood flow [CBF], resulting in brain ischemia and poor outcomes. Moreover, cerebral autoregulation is impaired after TBI, which prevents brain perfusion during systemic hypotension. Current Level II recommendations are to maintain systolic blood pressure > 70 + 2 (age) and CPP above 40 mmHg. Intravenous vasoactive agents such as phenylephrine (PHE), norepinephrine (NE), dopamine (DA) and epinephrine (EPI), while used to treat hypotension after correction with fluids/ blood products, lack comparison with respect to desired effect. Thus, initial choice of vasoactive agent is largely empiric, and variable. Importantly, vasoactive agents have not been compared vis-à-vis their effect on cerebral outcomes (hemodynamics [CPP] and perfusion [CBF and cerebral autoregulation]) after trauma; virtually nothing is known about their mechanisms or how these mechanisms relate to TBI. Our previous work suggests that knowing which intravenous vasoactive better corrects hypotension is clinically important, vasoactive agents differentially affect the neurovascular unit (NVU), and that the NVU plays an important role in cerebral perfusion and outcomes. Yet, no mechanisms for cerebral perfusion or dysautoregulation have been elucidated in pediatric trauma/TBI. The overarching hypothesis is that commonly used intravenous vasoactive agents have differential mechanistic effects on cerebral outcomes in TBI, and these differences are related to sex and age. The Specific Aims are to: 1) Examine the association between intravenously administered vasoactive agents (PHE, NE, DA, EPI) and cerebral perfusion (hemodynamics and autoregulation) after TBI by age and sex, and 2) Investigate the mechanism by which vasoactive agents (PHE, NE, DA, EPI) affect cerebral hemodynamics and autoregulation after TBI in children by age and sex. The impact of this exploratory R21 study will be to provide new information as to whether and how initial choice of vasoactive agent affects the NVU, cerebral hemodynamics and cerebral perfusion characteristics in pediatric TBI by age and sex.

 描述(申请人提供)：创伤是儿童和青少年的头号杀手，而创伤性脑损伤(TBI)是儿童创伤相关死亡的主要原因，男孩和幼儿的预后更差。在照顾受伤的儿童时，一线医生，如外科医生、麻醉师、急救内科医生和重症医生，经常努力预防和/或方便地纠正不必要的但普遍存在的低血压。这是有问题的，因为全身性低血压导致低脑灌注量(脑灌注压[CPP]和脑血流量[CBF]，从而导致脑缺血和不良预后。此外，颅脑损伤后的脑自动调节功能受损，从而在全身低血压时阻止脑灌流。目前的II级建议是保持收缩压&GT；70+2(年龄)和CPP在40毫米汞以上。静脉血管活性物质，如苯肾上腺素(Phe)、去甲肾上腺素(NE)、多巴胺(DA)和肾上腺素(EPI)，虽然用于治疗液体/血液制品纠正后的低血压，但缺乏与预期效果的比较。因此，血管活性物质的初始选择在很大程度上是经验性的，而且是可变的。重要的是，血管活性物质对创伤后脑部转归(血流动力学[CPP]和脑血流灌注[CBF和脑自动调节])的影响还没有被比较；几乎对它们的机制或这些机制与脑外伤的关系知之甚少。我们以前的工作表明，了解哪种静脉血管活性物质更好地纠正低血压具有临床重要性，血管活性物质对神经血管单位(NVU)的影响不同，NVU在脑血流灌注和预后中发挥重要作用。然而，在儿童创伤/脑损伤中，脑血流灌注或自身调节失调的机制尚未阐明。最重要的假设是，常用的静脉血管活性物质对脑损伤患者的脑预后有不同的机制影响，这些差异与性别和年龄有关。研究的具体目的是：1)研究脑损伤后静脉应用血管活性物质(Phe、NE、DA、EPI)与脑血流动力学和自身调节之间的年龄和性别相关性；2)探讨血管活性物质(Phe、NE、DA、EPI)对儿童颅脑损伤后脑血流动力学和自身调节的影响机制。这项探索性的R21研究的影响将是提供新的信息，即初始血管活性物质的选择是否以及如何影响年龄和性别对儿童脑外伤患者的NVU、脑血流动力学和脑血流灌注特性的影响。