Inhaled nitric oxide: Expanding indications beyond traditional boundaries

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that improves ventilation–perfusion matching with minimal effect on systemic blood pressure. Although the FDA approval is restricted to neonatal hypoxic respiratory failure associated with pulmonary hypertension, many clinicians now use iNO in adults with conditions where elevated pulmonary vascular resistance, right ventricular dysfunction threaten stability and hypoxic respiratory failure. This review examines both the mechanistic rationale and the available evidence for such off-label use. Examples range from acute RV failure in the ICU to perioperative support in cardiac surgery, heart and lung transplantation, and severe hypoxemic respiratory failure, including COVID-19–associated acute respiratory distress syndrome (ARDS). In these settings, iNO offers rapid afterload reduction and short-term improvement in oxygenation, but randomized trials are lacking and limited studies to date have failed to consistently show outcome benefits. Adverse effects such as methemoglobinemia, nitrogen dioxide toxicity, rebound pulmonary hypertension, and a potential increase in acute kidney injury risk in certain non-cardiac surgical populations. Additionally, cost considerations and other practical limitations must be weighed carefully. Overall, current evidence supports the use of iNO as an adjunctive therapy in carefully selected critically ill patients.