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.

“通过高流量鼻插管输送电化学产生的吸入一氧化氮 (iNO) （HFNC）” 抽象的 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 改善这些患者的氧合对于改善预后至关重要。 选择性肺血管扩张剂吸入一氧化氮（iNO）已成为强化治疗的支柱 用于治疗肺衰竭的护理单位以改善氧合，它也是一种非常有效的防腐剂。 通过无创高流量鼻插管 (HFNC) 方法进行 iNO 可能会消除以下需要： 并减少与有创机械通气相关的风险，我们勇敢地面对这一点。 HFNC 输送的水平到达肺部深处（NO 在此发挥其药理作用） 比通过低流量鼻插管输送的 NO 明显更大且更好控制。 目前的 iNO 技术成本过高，无法用于高流量吸入治疗。 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（最高 800 ppm）储存 NO 的气瓶，以防止歧化 我们开发了一种安全且极具成本效益的按需电化学方法。 我们利用稳定的无机亚硝酸钠溶液生成纯 NO，用于医疗应用。 现在将这项新技术与 HFNC 传输相结合并证明其可行性 这项新技术可在治疗相关的情况下安全、廉价地将 iNO 输送至肺部 如果成功，这项技术可能会改变 iNO 的范式。 在医疗机构中进行治疗，可用于更好地治疗由病毒或病毒引起的呼吸窘迫 细菌感染，例如 COVID-19。