Electrochemically Generated Inhaled Nitric Oxide (iNO) delivery via High Flow Nasal Cannula (HFNC)

通过高流量鼻插管 (HFNC) 输送电化学产生的吸入一氧化氮 (iNO)

• 批准号: 10637303
• 负责人: Gergely Lautner
• 金额: $ 46.13万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10637303
• 关键词: Acute Respiratory Distress Syndrome; Adult; Air; Animals; Antimicrobial Effect; Bacterial Infections; Blood; Breathing; COVID-19; COVID-19 complications; COVID-19 patient; Cannulas; Chronic; Clinical; Clinical Treatment; Clinical Trials; Coupled; Custom; Disease; Drug Delivery Systems; Ensure; FDA approved; Frequencies; Future; Gases; Generations; Goals; High Pressure Liquid Chromatography; Histopathology; Hypoxemia; Hypoxemic Respiratory Failure; In Vitro; Inductively Coupled Plasma Mass Spectrometry; Inhalation; Inhalation Drug Administration; Inhalation Therapy; Intensive Care Units; Intubation; Ions; Local Anti-Infective Agents; Lung; Masks; Mass Fragmentography; Mechanical ventilation; Medical; Medicine; Methemoglobin; Methods; Modeling; Monitor; Nitric Oxide; Nitrites; Nitrogen Dioxide; Nose; Oxygen; Oxygenators; Ozone; Patients; Pattern; Performance; Phase; Pulmonary Fibrosis; Pulmonary Hypertension; Reaction; Refractory; Respiratory Disease; Respiratory Tract Infections; Respiratory distress; Risk; Safety; Sedation procedure; Sheep; Sodium Nitrite; Spectroscopy, Fourier Transform Infrared; System; Technology; Testing; Therapeutic; Tidal Volume; Tube; Vasodilator Agents; Virus Diseases; acute hypoxemic respiratory failure; analytical method; cost; cost effective; endotracheal; feasibility testing; health care settings; hemodynamics; improved; improved outcome; in vivo Model; inhaled nitric oxide; lung failure; new technology; novel; operation; pharmacologic; porcine model; portability; pre-clinical; prevent; prototype; research clinical testing; respiratory; safety assessment; sheep model; ventilation; virtual; water vapor

"Electrochemically Generated Inhaled Nitric Oxide (iNO) Delivery via High Flow Nasal Cannula (HFNC)” Abstract Patients with COVID-19 or other severe respiratory tract infections often develop acute hypoxemic respiratory failure. Improving the oxygenation of these patients is critical for improving outcome. As a selective pulmonary vasodilator, inhaled nitric oxide (iNO) has already become a mainstay of intensive care units for lung failure to improve oxygenation and it is also a very potent antiseptic agent. Delivering iNO via a noninvasive high flow nasal cannula (HFNC) method can potentially obviate the need for, and reduce the risks associated with, invasive mechanical ventilation. We hypothesize that the NO levels delivered with HFNC reaching the deep lung - where NO has its pharmacological effect - would be significantly greater and better controlled than NO delivered via low flow nasal cannula. However, the costs of current iNO technologies are prohibitive for use in high flow inhalation therapy. These costs are associated with the long-term instability of NO and the limited payload of conventional NO gas cylinders in which NO must be stored at low concentrations (up to 800 ppm) to prevent disproportion reactions. We have developed a safe and very cost-effective electrochemical method for on-demand generation of pure NO from stable solutions of inorganic sodium nitrite for medical applications. We now propose to combine this novel technology with HFNC delivery and demonstrate the feasibility of this new technology for safe and inexpensive delivery of iNO to the lungs at therapeutically relevant levels via a nasal cannula. If successful, this technology can potentially shift the paradigm of iNO therapy in healthcare settings and could be used to better treat respiratory distress caused by viral or bacterial infections, such as in COVID-19.

“通过高流量鼻插管电化学产生的吸入一氧化氮（iNO）输送 （HFNC）” 摘要 患有COVID-19或其他严重呼吸道感染的患者通常会出现急性低氧血症 呼吸衰竭改善这些患者的氧合对于改善结局至关重要。作为 选择性肺血管扩张剂，吸入一氧化氮（iNO）已经成为一个支柱， 治疗肺衰竭的护理单位，以改善氧合，它也是一个非常有效的抗菌剂。提供 通过非侵入性高流量鼻插管（HFNC）方法的iNO可能会减少对以下方面的需求， 并降低与侵入性机械通气相关的风险。我们假设， HFNC到达肺深部时（NO具有药理学作用）， 与通过低流量鼻插管递送的NO相比，其显著更大且更好地控制。然而，在这方面， 当前iNO技术的成本对于在高流量吸入治疗中的使用是过高的。这些费用 与NO的长期不稳定性和常规NO气体的有限有效载荷有关 必须以低浓度（高达800 ppm）储存NO以防止不均衡的气瓶 反应.我们开发了一种安全且非常经济的电化学方法， 从无机亚硝酸钠的稳定溶液中产生纯NO用于医疗应用。我们 现在建议将这种新技术与HFNC输送相结合，并证明 这种新技术用于安全和廉价地将iNO输送到肺部， 通过鼻插管进行水平测量。如果成功，这项技术可能会改变iNO的模式。 治疗在医疗机构，并可用于更好地治疗呼吸窘迫引起的病毒或 细菌感染，如COVID-19。