Inhaled Nitric Oxide as a Treatment for Hypoxic Respiratory Failure

Inhaled nitric oxide (iNO) is a gas that is administered to patients through ventilation to help open up their lungs and improve oxygen levels in the blood. Nitric oxide is a naturally occurring molecule in the human body that helps to regulate blood flow and pressure in the lungs. It works by relaxing the smooth muscles found in the lungs, which helps dilate the blood vessels and improves ventilation of poorly oxygenated parts of the lung.

How does iNO work?

Nitric oxide acts as a vasodilator, meaning it causes blood vessels to relax and open up. When inhaled, the NO gas travels directly to the lungs where it binds to receptors on cells that line the blood vessels. This binding triggers a cascade of chemical reactions that ultimately lead to relaxation of vascular smooth muscle cells surrounding pulmonary arteries. The relaxation and dilation of these arteries decreases pulmonary hypertension and improves blood flow to poorly ventilated regions of the lung. By improving ventilation/perfusion matching, iNO therapy increases oxygen delivery to tissues and lowers pulmonary vascular resistance.

What conditions is iNO used to treat?

The primary FDA-approved use of  Inhaled nitric oxide is for term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension. It is also used off-label for treatment of pulmonary hypertension in adults and children. Some of the specific conditions iNO may be used for include:

- Respiratory distress syndrome (RDS) in premature newborns: RDS is caused by an immature lung surfactant system and causes poor gas exchange leading to hypoxia.

- Persistent pulmonary hypertension of the newborn (PPHN): A condition where elevated pulmonary vascular resistance impedes blood flow from the right ventricle to the lungs, causing oxygen levels to drop.

- Acute respiratory distress syndrome (ARDS) in adults and older children: ARDS develops when lung tissue becomes severely inflamed due to infection, trauma, or other direct lung injury causing hypoxemia.

- Congenital diaphragmatic hernia (CDH): A birth defect where the diaphragm fails to fully form, allowing abdominal organs to shift into the chest cavity and compress the lungs.

- Pulmonary hypertension associated with chronic lung disease: Conditions like bronchopulmonary dysplasia that involve long-term lung damage and abnormal blood vessel growth in the lungs.

How is iNO administered?

iNO is delivered through a specialized delivery system that blends a precise dose of NO gas with the ventilator gases being administered to the patient. The gas mixture is continuously delivered through the ventilator circuit via the endotracheal tube or breathing mask. Treatment is usually started at a low dose around 5 parts per million (ppm) and gradually titrated up based on the patient's response and NO levels. Continuous monitoring of oxygen saturation and blood gas measurements help guide dose adjustments. Typical treatment lasts from hours to days depending on the condition.

Monitoring the effects of iNO therapy

Close monitoring is required when using iNO to assess treatment effectiveness and potential toxicities. Parameters that may be followed include:

- Oxygen saturation levels measured by pulse oximetry: An immediate improvement of >5% generally indicates a positive response.

- Blood gas analysis: Periodic measurement of arterial blood gases will show increasing pO2 and decreasing pCO2 levels with good response.

- Echocardiography: May show a decrease in pulmonary artery pressures and improved cardiac function over the first 24 hours.

- Chest x-rays: Can assess whether lung inflation and aeration are improving.

- Biomarkers: B-type natriuretic peptide levels may fall with decreased cardiac stress from lower pulmonary pressures.

- Adverse effects: Methemoglobin and nitrogen dioxide levels are monitored to check for nitrosative stress.

Does iNO therapy work for all patients?

While studies have reported success rates around 50-70% in terms of acute oxygenation response, not all patients will benefit from iNO. Those less likely to respond positively include patients with severe hypoxemia, advanced lung disease, shock, or major air leaks/pneumothorax. Patients who have good lung compliance and recruitability but impaired gas exchange due to pulmonary vasoconstriction tend to do best. Around 30-40% may see no effect or may worsen on treatment. In non-responders, iNO is usually discontinued within the first 6 hours.

Potential risks and concerns

Along with its beneficial effects, there are risks associated with iNO therapy:

- Methemoglobinemia: Higher than safe levels of methemoglobin in red blood cells can impair oxygen delivery. This risk is mitigated by scavenger drugs and titrating to lower iNO doses.

- Formation of nitrogen dioxide (NO2): A toxic byproduct of iNO that can cause airway and lung inflammation at higher concentrations. Modern delivery systems carefully control NO2 levels.

- Cost: At around $1000 per treatment day, the cost of iNO limits its widespread use in resource-poor settings. Long-term benefit has also been difficult to prove.

Overall, iNO has become an established treatment for hypoxic respiratory failure in term and near-term newborns when used judiciously with close monitoring. While not all patients see benefit, it provides an important therapy for improving oxygen levels via selective pulmonary vasodilation in the right clinical context. Further research continues to better define its role and long-term outcomes.

Select the language you're most comfortable with

Japanese Korean

Get More Insights On Inhaled Nitric Oxide

About Author:

Alice Mutum is a seasoned senior content editor at Coherent Market Insights, leveraging extensive expertise gained from her previous role as a content writer. With seven years in content development, Alice masterfully employs SEO best practices and cutting-edge digital marketing strategies to craft high-ranking, impactful content. As an editor, she meticulously ensures flawless grammar and punctuation, precise data accuracy, and perfect alignment with audience needs in every research report. Alice's dedication to excellence and her strategic approach to content make her an invaluable asset in the world of market insights.

(LinkedIn: www.linkedin.com/in/alice-mutum-3b247b137 )