From the Guidelines
Nitric oxide plays a crucial role in Acute Respiratory Distress Syndrome (ARDS) as a therapeutic agent that can improve oxygenation, but it has not been shown to significantly affect mortality. As a treatment, inhaled nitric oxide (iNO) can be administered to selectively dilate pulmonary vessels in ventilated lung regions, improving ventilation-perfusion matching and oxygenation in ARDS patients 1. The benefits of iNO include:
- Lowering pulmonary artery pressures
- Improving right ventricular function in patients with pulmonary hypertension
- Reducing edema formation in patients with ALI/ARDS through effects on hydrostatic pressure However, the clinical benefits of iNO are typically transient, and it has not been found to significantly affect mortality 1. Endogenously, nitric oxide serves as a signaling molecule that regulates vascular tone, inflammation, and cellular injury during ARDS. The use of iNO therapy should be reserved for severe cases as a rescue therapy or bridge to other interventions rather than as a standard treatment. Key considerations for iNO therapy include:
- Doses of 5-20 parts per million
- Selective vasodilation without causing systemic hypotension
- Transient clinical benefits, typically lasting 24-48 hours
- Limited impact on overall ARDS outcomes, despite short-term benefits for oxygenation 1.
From the FDA Drug Label
In a randomized, double-blind, parallel, multicenter study, 385 patients with adult respiratory distress syndrome (ARDS) associated with pneumonia (46%), surgery (33%), multiple trauma (26%), aspiration (23%), pulmonary contusion (18%), and other causes, with PaO2/FiO2 <250 mm Hg despite optimal oxygenation and ventilation, received placebo (n=193) or INOmax (n=192), 5 ppm, for 4 hours to 28 days or until weaned because of improvements in oxygenation. Despite acute improvements in oxygenation, there was no effect of INOmax on the primary endpoint of days alive and off ventilator support. INOmax is not indicated for use in ARDS.
The role of nitric oxide in ARDS is that it provides acute improvements in oxygenation, but it does not have a significant effect on the primary endpoint of days alive and off ventilator support. The use of INOmax is not indicated for ARDS 2.
- Key points:
- Nitric oxide improves oxygenation in ARDS patients
- No effect on days alive and off ventilator support
- Not indicated for use in ARDS
From the Research
Role of Nitric Oxide in ARDS
- Nitric oxide (NO) has been shown to improve oxygenation in patients with acute respiratory distress syndrome (ARDS) 3, 4, 5.
- Inhaled NO (iNO) has been recommended as rescue therapy in ARDS cases, particularly in patients with severe ARDS due to COVID-19 pneumonia 3.
- The administration of iNO has been associated with an increase in oxygenation, as measured by the PaO2/FiO2 ratio, in select patients with ARDS 4, 5.
- The optimal dose of iNO for improving oxygenation in ARDS patients is unclear, but doses ranging from 1-20 parts per million (ppm) have been shown to be effective 4, 5, 6.
Mechanism of Action
- iNO selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with ARDS 5.
- The decrease in pulmonary vascular resistance during iNO inhalation correlates with the level of pulmonary vascular resistance without NO 5.
- The reduction of venous admixture correlates with the level of venous admixture without NO 5.
Clinical Use
- iNO may be considered as adjunct therapy to tentatively improve oxygenation in patients with severely hypoxemic ARDS 7.
- However, the current evidence suggests that iNO should not be routinely used in patients with ARDS, as it has not been shown to decrease mortality or improve outcomes 7.
- Long-term iNO inhalation at low concentrations may be effective in reducing mean pulmonary artery pressure and improving arterial oxygen tension in patients with ARDS, without evidence of tachyphylaxis 5, 6.