Treatment of Cerebral Edema using Ventricular Therapy

描述（由申请人提供）：脑水肿与创伤性脑损伤相关。提出的干预措施的总体假设是，创伤性损伤后从脑中清除游离水将使脑水肿最小化。方法：申请人提议完成用于减少脑水肿的创新导管的临床前开发。该导管的初始临床应用将是创伤性脑损伤，并将涉及用除水治疗（WRT）导管替换标准脑室引流管，该导管1）从CS中清除游离水，2）清除大量脑脊液（CSF）样本，3）监测颅内压。去除游离水将增加CSF的渗透压，这在理论上将导致间质脑水的去除和营养交换的改善，从而改善脑灌注。I期研究表明，人CSF渗透压随创伤性脑损伤而增加，WRT导管可以临床显著速率从CSF中清除水分，从而改善离体绵羊脑组织中的水分运动。具体目的：（1）在体外构建和测试WRT导管，以满足人体研究要求。(2)在无损伤猪模型中对WRT导管进行体内试验。这些测试将确定器械在不同操作参数下的安全性。(3)在猪模型中，在冷冻损伤后，测量脑变化（压力和肿胀）以及使用心室WRT导管治疗的功能结局。将进行急性（6小时）和慢性（1周）随机对照损伤研究。重要性：创伤性损伤和严重中风后的脑水肿是一种危及生命的疾病，在相当多的患者群体中常规治疗难以治愈。目前的治疗（即过度换气，渗透剂或体温过低）与严重的副作用有关，这些副作用随着长期使用而增加。第二阶段目标的成功完成将使WRT导管的人体研究成为可能。

DESCRIPTION (provided by applicant): Cerebral edema is associated with traumatic brain injury. The overall HYPOTHESIS of the proposed intervention is that free water removed from the brain following traumatic injury will minimize cerebral edema. Approach: The applicant proposes to complete preclinical development of an innovative catheter for the reduction of cerebral edema. The initial clinical application of this catheter will be traumatic brain injury, and will involve replacing standard ventricular drains with Water Removal Therapy (WRT) catheters that 1) remove fee water from the CS, 2) remove bulk cerebral spinal fluid (CSF) samples, and 3) monitor intracranial pressure. Removal of water free will increase osmolarity of the CSF, which will theoretically result in removal of interstitial brain water and improved nutrient exchange, creating improved cerebral perfusion. Phase I studies have demonstrated that human CSF osmolarity increases with traumatic brain injury and WRT catheters can remove water from CSF at clinically significant rates that improves water movement in ex vivo ovine cerebral tissue. Specific Aims: (1) Build and test WRT catheters in vitro to meet human study requirements. (2) Test WRT catheters in vivo in a non-injury swine model. These tests will establish device safety under different operating parameters. (3) Measure cerebral changes (pressure and swelling) and functional outcome with ventricular WRT catheter treatment in vivo after cold freeze injury in swine model. Acute (6 hours) and chronic (1 week) randomized controlled injury studies will be undertaken. Significance: Cerebral edema after traumatic injury and severe stroke is a life threatening condition that is refractory to conventional treatments in a significant population of patients. Current treatments (i.e. hyperventilation, osmotic agents, or hypothermia) are associated with serious side effects that increase with prolonged use. Successful completion of Phase II aims will make human studies of WRT catheters possible.