• Clinical Info

Uses

Neonatal Hypoxic Respiratory Failure

Used in conjunction with ventilatory support and other appropriate therapy to improve oxygenation and reduce the need for extracorporeal membrane oxygenation (ECMO) in term or near-term (>34 weeks of age) neonates with hypoxic respiratory failure and clinical or ECG evidence of pulmonary hypertension.

Most effective in patients with severe persistent pulmonary hypertension who have minimal underlying parenchymal lung disease (idiopathic persistent pulmonary hypertension).

Least effective in neonates with pulmonary hypoplasia (e.g., congenital diaphragmatic hernia).

Has been used with good results (i.e., decreased the incidence of severe intraventricular hemorrhage and periventricular leukomalacia) in premature neonates† (<34 weeks’ gestation) who were undergoing mechanical ventilation for respiratory distress syndrome.

Dosage and Administration

General

• Precise monitoring of nitrogen dioxide, nitric oxide, and oxygen (partial pressure of arterial oxygen [PaO₂]) concentrations should be performed. Periodic measurement of methemoglobin also recommended. (See Methemoglobinemia under Cautions.)

Administration

Oral Inhalation

Administer in conjunction with mechanical ventilation and other supportive therapy to maximize oxygen delivery. In neonates with collapsed alveoli, administer additional therapies to improve lung expansion (e.g., pulmonary surfactant replacement, high-frequency oscillatory ventilation).

Administer by inhalation using a nitric oxide delivery system that provides operator-determined and constant concentrations of nitric oxide throughout the respiratory cycle, does not cause generation of excessive nitrogen dioxide, and is equipped with appropriate alarms.

Delivery system should include a backup battery power supply to ensure continuous administration during a power failure.

Dosage

Pediatric Patients

Neonatal Hypoxic Respiratory Failure

Oral Inhalation

Term or near-term neonates (>34 weeks of age): 20 ppm given continuously for up to 14 days or until the underlying oxygen desaturation has resolved and the patient is ready to be weaned from therapy.

Weaning and Discontinuance of Therapy

Oral Inhalation

Following improvement in oxygenation, smaller maintenance dosages (5–6 ppm) have been used. Therapy can be discontinued after successful maintenance of oxygenation at reduced dosage (5–6 ppm).

Dosage also can be reduced stepwise in increments as little as 1 ppm.

If clinical deterioration during the weaning period occurs, the nitric oxide dosage and/or inspired oxygen concentration fraction (FiO₂) may be increased transiently. If clinical deterioration occurs after discontinuance of therapy, temporarily reinstitute therapy at the last dosage used.

Prescribing Limits

Pediatric Patients

Neonatal Hypoxic Respiratory Failure

Oral Inhalation

Dosages >20 ppm generally do not provide additional benefit, are associated with an increased incidence of adverse effects, and generally are not recommended.

Cautions

Contraindications

• Neonates dependent on extrapulmonary right-to-left shunting of blood (e.g., ductal-dependent congenital heart disease).

Warnings/Precautions

General Precautions

Withdrawal of Therapy

Abrupt discontinuance of nitric oxide therapy can result in oxygen desaturation and a rebound increase in pulmonary artery pressure. Such manifestations also can occur in neonates who do not respond to inhaled nitric oxide therapy.

To minimize adverse effects associated with withdrawal of therapy, neonates should be weaned from therapy by a gradual reduction in dosage and should be monitored for evidence of deterioration during and after weaning. (See Weaning and Discontinuation of Therapy under Dosage and Administration.)

Methemoglobinemia

Possible dose-related methemoglobinemia; occurs infrequently with usual recommended dosages, but was observed in 35% of neonates receiving a higher dosage (80 ppm). Methemoglobin concentrations generally return to baseline within several hours following dosage adjustment or discontinuance of therapy.

Monitor methemoglobin blood concentrations periodically (e.g., within 4 hours of initiating therapy and daily thereafter). Methemoglobinemia that does not resolve after adjustment of nitric oxide dosage may be treated with IV vitamin C, IV methylene blue, or blood transfusion as clinically appropriate.

Nitrogen Dioxide Accumulation

Possible formation of nitrogen dioxide: Recommended dosages resulted in formation of a small amount of nitrogen dioxide (<0.5 ppm); however, a larger dosage (80 ppm) resulted in a mean peak concentration of nitrogen dioxide of 2.6 ppm.

Nitrogen dioxide may interact with oxyhemoglobin to form methemoglobin; exposure to elevated nitrogen dioxide concentrations also can cause acute lung injury.

The Occupational Safety and Health Administration (OSHA) has set exposure limits for nitric oxide of 25 ppm and for nitrogen dioxide of 5 ppm.

Specific Populations

Pregnancy

Category C. Not intended for use in adults.

Lactation

Not known whether nitric oxide is distributed into milk; use not indicated in nursing women.

Pediatric Use

Manufacturer does not recommend use in neonates with chronological age of >14 days or gestational age of <34 weeks. However, in a clinical study, beneficial effects have been shown in premature neonates (<34 weeks’ gestation) with respiratory distress syndrome who received inhaled nitric oxide therapy while undergoing mechanical ventilation.

ARDS

Not indicated in patients with ARDS.

Common Adverse Effects

Hypotension, withdrawal manifestations (e.g., increased pulmonary artery pressure, decreased PaO₂, increase in or return to right-to-left shunting of blood, atelectasis, hematuria, hyperglycemia, sepsis, infection, stridor, cellulitis.

Last Updated: July 01, 2006