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）是儿科创伤相关死亡的主要原因，其中男孩和幼儿的结局更糟。在照顾受伤的儿童时，外科医生、麻醉师、急诊科医生和重症监护医师等一线医生经常努力预防和/或迅速纠正不必要的但普遍的低血压。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[CPP]和脑血流量[CBF]），导致脑缺血和预后不良。此外，TBI后脑自动调节功能受损，这会阻碍全身性低血压期间的脑灌注。目前的II级建议是维持收缩压> 70 + 2（年龄）和CPP高于40 毫米汞柱。静脉注射血管活性药物如去氧肾上腺素（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，但在预期效果方面缺乏比较。因此，血管活性剂的最初选择很大程度上是经验性的，并且是可变的。重要的是，血管活性 尚未比较药物对创伤后脑结局（血流动力学 [CPP] 和灌注 [CBF 和脑自动调节]）的影响；事实上，人们对它们的机制或这些机制与 TBI 的关系一无所知。我们之前的工作表明，了解哪种静脉注射血管活性药物能更好地纠正低血压在临床上很重要，血管活性药物对血压的影响存在差异。 神经血管单元（NVU），并且 NVU 在脑灌注和结果中起着重要作用。然而，尚未阐明儿科创伤/TBI 中脑灌注或自身调节障碍的机制。总体假设是，常用的静脉注射血管活性药物对 TBI 的脑结局具有不同的机制影响，并且 这些差异与性别和年龄有关。具体目标是： 1) 按年龄和性别检查静脉注射血管活性药物（PHE、NE、DA、EPI）与 TBI 后脑灌注（血流动力学和自动调节）之间的关系，以及 2) 研究血管活性药物（PHE、NE、DA、EPI）影响 TBI 后脑血流动力学和自动调节的机制。 按年龄和性别划分的儿童 TBI。这项探索性 R21 研究的影响将是提供关于血管活性药物的初始选择是否以及如何影响年龄和性别儿童 TBI 的 NVU、脑血流动力学和脑灌注特征的新信息。