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（由适用提供）：创伤是儿童和青少年的主要杀手，脑外伤（TBI）是小儿创伤与死亡有关的主要原因，男孩和幼儿的结果较差。在为受伤的儿童带来时，前线医生，例如外科医生，麻醉医生，急诊医生和强化学家，通常会努力预防和/或极为纠正不需要但普遍的低血压。这是有问题的，因为全身性低血压会导致低脑灌注（脑灌注压力[CPP]和大脑血流[CBF]，导致大脑缺血和不良的结局。此外，脑自动调节受到脑自动训练，在TBI后会损害TBI，这会在TBI后造成损害，这会在当前的级别上进行propersife + Symitive。 MMHG。 （血液动力学[CPP]和灌注[CBF和脑自动调节]）在创伤之后；实际上，他们的机制几乎没有任何了解，或者这些机制与我们先前的工作如何相关。脑灌注和结局。然而，在小儿创伤/TBI中，尚未阐明脑灌注或功能障碍调节的机制。总体假设是，常用的静脉输液血管活性剂对TBI的脑结局具有不同的机械作用，而这些差异与性别和年龄有关。 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.这项探索性R21研究的影响是提供有关血管活性剂的最初选择以及如何影响NVU，脑血动力学和脑灌注特征在儿科TBI中按年龄和性别中的脑灌注特征的新信息。