Veno-venous extracorporeal blood phototherapy as treatment for carbon monoxide poisoning

静脉-静脉体外血液光疗治疗一氧化碳中毒

• 批准号: 425351607
• 负责人: Dr. Anna Fischbach
• 金额: --
• 依托单位: Department of Anesthesia, Critical Care and Pain Medicine
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/425351607?language=en
• 关键词: Veno; venous; extracorporeal; blood; phototherapy

Carbon monoxide (CO) intoxication is a leading cause of poisoning related death and results in more than 20,000 visits to emergency departments in the United States each year. The mortality rate from CO poisoning is 1 – 3% and the rate of morbidity is as high as 40%. Patients who survive CO poisoning suffer from neurologic and cardiac sequelae, which have been shown to increase the long-term mortality. If one considers both hospital costs and lost earnings, the economic burden of CO intoxication is approximately 1.3 billion dollars each year. The toxicity associated with inhalation of CO is caused by the impairment of oxygen delivery to, and inhibition of ATP generation in, mitochondria. Compared to oxygen, CO has a 250-fold higher affinity for the binding site in hemoglobin (Hb) resulting in tissue hypoxia. The main goal of treatment for CO poisoning is to remove CO from the body as quickly as possible by oxygen. Through competitive binding of oxygen to Hb, CO is displaced from Hb in the lung and then exhaled. The CO t1/2 while breathing room air, 100% oxygen or hyperbaric oxygen is approximately 5 hours, 2 hours and 30 minutes respectively. Unfortunately, hyperbaric oxygen therapy is often delayed, because of the need to transport the patient to medical centers with specialized equipment. Furthermore, hyperbaric oxygen may be complicated by barotrauma, oxygen toxicity, seizures and pulmonary edema. Because of these limitations to the current treatment of patients with CO poisoning, new therapies are needed to improve outcomes.The overall objective of the current proposal is to design and develop a large artificial lung unit that combines the principles of CO photodissociation and extra-corporeal oxygenation to increase the rate of CO removal from patients with CO poisoning. In preliminary studies led by Drs. Zazzeron and Zapol, we designed and built a small photo- extracorporeal CO removal (ECCOR) device that increased the rate of CO removal from CO-poisoned rats. However, the prototypic device will require modifications to permit treatment of larger animals and ultimately patients with CO poisoning. The required changes include larger surface areas for gas exchange and illumination and the ability to accommodate a higher blood flow rate. After in-vitro testing of oxygenating performance and CO removal, the ability of the photo-ECCOR device to remove CO from blood will be tested in a sheep model of CO poisoning.By the end of this research fellowship, I anticipate that we will have a prototypic veno-venous photo-ECCOR device that can efficiently remove CO from the blood of large animals, including humans.

一氧化碳(CO)中毒是与中毒相关的死亡的主要原因，每年导致美国2万多人去急诊科就诊。一氧化碳中毒的死亡率为1-3%，发病率高达40%。CO中毒后存活的患者会出现神经系统和心脏后遗症，这已被证明会增加长期死亡率。如果同时考虑住院费用和收入损失，每年一氧化碳中毒的经济负担约为13亿美元。与吸入CO相关的毒性是由于向线粒体输送氧气的障碍和抑制线粒体内ATP的生成所致。与氧相比，一氧化碳对导致组织缺氧的血红蛋白(Hb)中的结合部位具有250倍的亲和力。治疗一氧化碳中毒的主要目的是通过氧气尽快将一氧化碳从体内排出。通过氧与Hb的竞争性结合，一氧化碳在肺内从Hb中转移出来，然后呼出。呼吸室内空气、100%氧气和高压氧时的CO_(1/2)分别约为5小时、2小时和30分钟。不幸的是，高压氧治疗经常被推迟，因为需要用专门的设备将患者送到医疗中心。此外，高压氧可能会并发气压伤、氧中毒、癫痫发作和肺水肿。由于目前对一氧化碳中毒患者的治疗存在这些局限性，需要新的治疗方法来改善结果。本方案的总体目标是设计和开发一种结合一氧化碳光解离和体外氧合原理的大型人工肺单元，以提高一氧化碳中毒患者的一氧化碳清除率。在Zazzeron博士和Zapol博士领导的初步研究中，我们设计并建造了一种小型光体外CO清除装置(ECCOR)，它可以提高CO中毒大鼠的CO清除速度。然而，原型设备需要进行修改，以允许治疗较大的动物，并最终治疗一氧化碳中毒患者。所需的改变包括更大的气体交换和照明表面积，以及适应更高的血流速度的能力。在体外测试氧合性能和CO去除后，将在一氧化碳中毒的绵羊模型上测试光-ECCOR装置从血液中去除CO的能力。在本次研究结束时，我预计我们将拥有一个原型静脉-静脉-光-ECCOR装置，它可以有效地从包括人类在内的大型动物的血液中去除CO。

项目成果

Phototherapy and extracorporeal membrane oxygenation facilitate removal of carbon monoxide in rats

• DOI: 10.1126/scitranslmed.aau4217
• 发表时间: 2019-10
• 期刊: Science Translational Medicine
• 影响因子: 17.1
• 作者: L. Zazzeron;A. Fischbach;W. Franco;W. Farinelli;F. Ichinose;D. Bloch;R. R. Anderson-R.;W. Zapol

Hyperbaric phototherapy augments blood carbon monoxide removal

• DOI: 10.1002/lsm.23486
• 发表时间: 2021-10-17
• 期刊: LASERS IN SURGERY AND MEDICINE
• 影响因子: 2.4
• 作者: Fischbach, Anna;Traeger, Lisa;Zapol, Warren M.
• 通讯作者: Zapol, Warren M.

A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects.

一种新型吸入面罩系统，可为自主呼吸受试者提供高浓度一氧化氮

• DOI: 10.3791/61769
• 发表时间: 2021
• 期刊: Journal of visualized experiments : JoVE
• 作者: Pinciroli R;Traeger L;Fischbach A;Gianni S;Morais CCA;Fakhr BS;Di Fenza R;Robinson D;Carroll R;Zapol WM;Berra L
• 通讯作者: Berra L