HYPERVENTILATION ON CEREBRAL BLOOD FLOW/BRAIN OXYGENATION IN BRAIN INJURY

脑损伤时过度通气对脑血流/脑氧合的影响

• 批准号: 6494883
• 负责人: MICHAEL N DIRINGER
• 金额: $ 38.25万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6494883
• 关键词: adult human (21+); bioenergetics; blood flow measurement; brain circulation; brain injury; cerebral ischemia /hypoxia; clinical research; hemodynamics; high frequency ventilation; human subject; human therapy evaluation; intracranial pressure; pathologic process; positron emission tomography; respiratory oxygenation

Each year approximately 2 million people suffer traumatic brain injuries (TBI) in the U.S. Of these about 100,000 die and 90,000 are left with long-term disabilities. Advances in the management of these patients have reduced mortality but done little to ameliorate brain injury. Recent studies in severe TBI patients have suggested that reduced regional cerebral blood flow (rCBF) in the first few hours after injury contributes to secondary brain injury. Additionally, the use of acute hyperventilation (HV) to treat elevated intracranial pressure following TBI may led to or exacerbate ischemia thus augmenting rather than preventing secondary CNS injury. In order to understand the impact of HV on brain oxygenation, it is important to determine if the reduction in rCBF seen in TBI patients produces brain oxygen deprivation severe enough to cause ischemic neuronal damage. The presence of a PET scanner in the NNICU at Barnes-Jewish Hospital, combined with our extensive experience with the use of PET to detect ischemia, our expertise in the clinical management of TBI patients, and the large available patient population gives us a unique opportunity to address these issues. We propose to investigate the impact of acute HV on cerebral blood flow and brain oxygenation in TBI. Specifically we will test the hypothesis that severe (PaCO2 of about 25 mm Hg) but not moderate (PaCO2 of about 30 mm Hg) hyperventilation following TBI can produce reduction in CBF potentially severe enough to cause cerebral energy failure (defined as CBF that is insufficient to meet metabolic needs). We will study 30 patients within 12 hours of non-penetrating severe head injury (GCS less then or equal of 8) who have just completed PET measurements of regional (CBF, CMRO2, OEF2 A-VDO2 and CvO3 as part of project 1. Patients with elevated ICP(18 - 25 mm Hg) at the time of the initial PET study will have repeat PET measurements of rCBF and CMRO2, OEF, A-VDO2, and CvO2, again after acute HV, Three groups of 10 patients each will be studied. The first group will have PaCPO2 lowered to 30+2 torr. If no patient develops cerebral ischemia potentially severe enough to cause energy failure the second group will have PaCO2 lowered to 25+2 torr. Otherwise, the second group will have PaCO2 lowered, in those patients with an initial PaCO2 greater then or equal to 35 torr, to 35=2 torr to determine if there is a safe threshold for HV. A third group of ten patients will serve as non- hyprventilated controls. These investigations are critical to determine the proper use of HV in the treatment of acute TBI.

每年约有200万人遭受创伤性脑损伤 (TBI)在美国，大约10万人死亡，9万人幸存 长期残疾。在这些患者的管理方面取得了进展 降低了死亡率，但对改善脑损伤几乎没有什么作用。近期 对重型颅脑损伤患者的研究表明，局部减少 损伤后头几小时的脑血流量(RCBF)对 继发性脑损伤。此外，使用急性 过度换气(HV)治疗继发性高颅压 颅脑损伤可能导致或加剧缺血，从而增加而不是 预防中枢神经继发性损伤。为了了解HV的影响 在脑氧合方面，重要的是要确定脑氧合的减少 颅脑损伤患者的rCBF导致严重的脑缺氧 造成缺血性神经元损伤。正电子发射计算机断层扫描仪出现在 巴恩斯犹太医院的NNICU，结合我们丰富的经验 随着PET用于检测缺血，我们在临床上的专业知识 脑外伤患者的管理，以及庞大的可用患者群体 这为我们提供了一个解决这些问题的独特机会。我们建议 探讨急性HV对脑血流量和脑组织的影响 创伤性脑损伤的氧合作用。具体地说，我们将测试这一假设 (PaCO2约为25毫米汞)但不适中(PaCO2约为30毫米汞) 颅脑损伤后过度换气可能导致脑血流量减少 严重到足以导致大脑能量衰竭(定义为CBF，即 不足以满足新陈代谢需求)。我们将研究30名患者 12小时非穿透性重型颅脑损伤(GCS小于或等于 8)刚刚完成区域(CBF、CMRO2、OEF2)的PET测量 作为项目1一部分的A-VDO2和CvO_3。颅内压升高的患者(18-25 毫米汞柱)在最初的PET研究时将有重复的PET 急性发作后再次测定rCBF、CMRO2、OEF、A-VDO2和CvO2 HV，将进行三组研究，每组10名患者。第一组 PaCPO2将降至30+2托。如果没有患者出现脑部疾病 缺血可能严重到足以导致第二次能量衰竭 组将PaCO2降至25+2托尔。否则，第二组 在那些初始PaCO2较高的患者中，PaCO2将会降低 则等于或等于35托，等于35=2托，以确定是否有保险箱 HV的门槛。第三组10名患者将作为非 过度换气控制。这些调查对于确定 HV在急性颅脑损伤治疗中的合理应用