PHYSIOLOGIC RESPONSE TO OSMOTIC THERAPY IN BRAIN EDEMA

脑水肿对渗透疗法的生理反应

• 批准号: 6795651
• 负责人: MICHAEL N DIRINGER
• 金额: $ 24.57万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6795651
• 关键词: acute disease /disorder; blood brain barrier; blood volume; body fluid osmolarity; body water; brain circulation; brain edema; brain injury; brain morphology; cerebral hemorrhage; clinical research; drug screening /evaluation; human subject; human therapy evaluation; intracranial pressure; magnetic resonance imaging; mannitol; medical complication; membrane permeability; nervous system disorder therapy; osmotic pressure; positron emission tomography; saline; stroke

Acute brain injury is complicated by mass effect, a major cause of secondary injury by critically reducing cerebral perfusion pressure or producing tissue shifts which can lead to herniation. While the etiology and mechanisms responsible for this mass effect may differ considerably depending on the clinical condition, treatment options are limited. Traditionally osmotic agents have been the mainstay of medical treatment employing mannitol and recently hypertonic saline solutions. Despite numerous investigations and mannitors ubiquitous use, considerable controversy persists regarding its 1) mechanism of action (whether it reduces cerebral blood volume [CBV] or brain water), 2) differential effect in normal and abnormal brain, 3) effect on cerebral blood flow (CBF) and oxygen metabolism (CMRO2), 4) loss of efficacy over time, and 5) uptake into injured brain, which could lead to "rebound edema." In part because of some of these concerns, hypertonic saline (HS) has been introduced as an alternative agent; however, its physiologic effect and clinical efficacy compared to mannitol is unknown. Optimal use of these osmotic agents to treat brain swelling requires a detailed knowledge of their physiological effects in human subjects under the clinical conditions in which they are used. To this end, we will carry out the following Specific Aims: 1) measure the effect of a single bolus of mannitol or HS (23.4%) on regional CBF, CMRO2, CBV in patients with traumatic brain injury (TBI) and large hemispheric infarctions (LHI). We will measure CBF, CBV and CMRO2 using PET before and after a bolus of equi-osmolar (5.49 mOsm/kg ) doses of mannitol (1.0 gm/kg ) or HS (0.686 ml/kg), in 10 patients each with LHI and midline shift and 10 patients each with severe TBI; 2) measure the effect of a single bolus of mannitol or HS (23.4%) on regional brain volume in patients with LHI. In 20 patients we will measure regional change in brain volume using MRI before and after the same doses of mannitol and HS used in Aim 1. TBI patients will not be studied due to the MRI incompatibility of ICP monitors; 3) measure the extent that mannitol crosses the blood-brain-barrier in patients with TBI and LHI receiving osmotic therapy. In 15 patients with each entity we will measure blood: brain permeability of mannitol using PET and carbon-11 labeled-mannitol.

急性脑损伤并发质量效应，这是继发性损伤的主要原因，通过严重降低脑灌注压或产生可导致脑疝的组织移位。虽然病因学和机制负责这种质量效应可能会有很大的不同，这取决于临床条件，治疗选择是有限的。传统上渗透剂一直是采用甘露醇和最近高渗盐溶液的医学治疗的支柱。尽管有大量的研究和甘露醇的普遍使用，但关于其1）作用机制（是否减少脑血容量[CBV]或脑水），2）在正常和异常脑中的差异效应，3）对脑血流量（CBF）和氧代谢（CMRO 2）的影响，4）随着时间的推移疗效丧失，以及 5)吸收到受伤的大脑，这可能导致“反弹性水肿"。部分由于这些问题，高渗盐水（HS）已被引入作为替代药物;然而，与甘露醇相比，其生理作用和临床疗效尚不清楚。这些渗透剂治疗脑肿胀的最佳用途需要详细了解其在使用它们的临床条件下对人类受试者的生理作用。为此，我们将进行以下具体目标：1）测量单次推注甘露醇或HS（23.4%）对创伤性脑损伤（TBI）和大面积半球梗死（LHI）患者局部CBF、CMRO 2、CBV的影响。我们将使用PET测量等渗透压推注前后的CBF、CBV和CMRO 2（5.49 mOsm/kg）剂量的甘露醇（1.0克/千克）或统一制度（0.686 ml/kg），LHI、中线移位各10例，重度TBI各10例; 2）测量单次推注甘露醇或HS（23.4%）对患有脑梗死患者局部脑容量的影响， LHI。在20例患者中，我们将使用MRI测量目标1中使用的相同剂量的甘露醇和HS前后的脑体积局部变化。由于ICP监测器的MRI不兼容性，将不研究TBI患者; 3）测量接受渗透治疗的TBI和LHI患者中甘露醇穿过血脑屏障的程度。在15例患者中，我们将使用PET和碳-11标记的甘露醇测量甘露醇的血脑渗透性。