Inhaled nitric oxide acutely and locally relaxes constricted pulmonary vascular smooth muscle, resulting in decreased pulmonary vascular resistance, but it generally does not cause hemodynamic changes outside the lung. Additionally, inhaled nitric oxide may improve arterial oxygenation in hypoxemic patients by reducing intrapulmonary shunt and improving ventilation-perfusion matching. In both pediatric and adult patients, inhaled nitric oxide has been studied and used as a treatment modality in the intensive care unit (ICU) setting for a large number of clinical conditions in which reduction of pulmonary vascular resistance and/or improvement in arterial oxygenation is desired, including persistent pulmonary hypertension of the newborn; congenital diaphragmatic hernia; premature infant respiratory failure; respiratory distress syndrome (adults and children); cystic fibrosis; sickle cell disease; primary pulmonary hypertension; postoperative congenital heart disease; one-lung ventilation during thoracic surgery; postpneumonectomy; lung transplantation ischemia/reperfusion injury; and perioperative pulmonary hypertension associated with cardiac transplantation and left ventricular assist device implantation. Multiple outcome parameters have been measured to show inhaled nitric oxide treatment efficacy for the various clinical conditions listed above, but results have varied, yielding both positive and negative findings. However, it is safe to say that there is currently no evidence that inhaled nitric oxide therapy improves long-term morbidity or mortality rates for any clinical condition studied, and any short-term benefits of instituting inhaled nitric oxide therapy must be weighed against the known acute and potential long-term toxic effects of inhaled nitric oxide. The current Food and Drug Administration (FDA)–approved use for inhaled nitric oxide (marketed as INOmax) is for the treatment of term and near-term (>34 weeks) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension, where it improves oxygenation and reduces the need for extracorporeal membrane oxygenation. Thus, all other off-label indications for inhaled nitric oxide are regulated at the institutional level.

Because of the short half-life of nitric oxide, sustained pulmonary vasodilatation requires continuous delivery of inhaled nitric oxide via
commercially available systems that accurately deliver inspired concentrations between 1 and 80 parts per million (ppm). These systems must be able to deliver a constant concentration of inhaled nitric oxide to patients while minimizing the generation of nitrogen dioxide (NO₂), a direct toxin and environmental pollutant, as well as continuously monitor inspired NO, NO₂, and O₂ concentrations. Clinically significant levels of NO₂ are unlikely to occur when inhaled nitric oxide is delivered by an efficient delivery system at concentrations of 20 ppm or less. Inhaled NO is usually delivered during mechanical ventilation into the inspiratory limb of the ventilatory circuit by either pulse or continuous modes, although it may be administered to spontaneously breathing patients with a close-fitting mask.