Nitric OxideU.S. Brand Names: INOmax�(r)
Generic Available: No
Canadian Brand Names: INOmax�(r)
Use: Treatment of term and near-term (>34 weeks) neonates with hypoxic respiratory failure associated with pulmonary hypertension; used concurrently with ventilatory support and other agents
Use - Unlabeled/Investigational: Treatment of adult respiratory distress syndrome (ARDS)
Pregnancy Risk Factor: C
Pregnancy Implications: Reproduction studies have not been conducted.
Lactation: Excretion in breast milk unknown
Contraindications: Hypersensitivity to nitric oxide or any component of the formulation; neonates dependent on right-to-left shunting of blood
Warnings/Precautions: Abrupt discontinuation may lead to worsening hypotension, oxygenation, and increasing pulmonary artery pressure (PAP). Worsening oxygenation and increasing PAP may occur in patients who do not respond. Doses above 20 ppm should not be used because of the increased risk of methemoglobinemia and elevated nitrogen dioxide (NO2) levels. Methemoglobin levels and NO2 should be monitored.
Adverse Reactions: >10%: Cardiovascular: Hypotension (13%) Miscellaneous: Withdrawal syndrome (12%) 1% to 10%: Dermatologic: Cellulitis (5%) Endocrine & metabolic: Hyperglycemia (8%) Genitourinary: Hematuria (8%) Respiratory: Atelectasis (9% - same as placebo), stridor (5%) Miscellaneous: Sepsis (7%), infection (6%) Postmarketing and/or case reports: Headache (environmental exposure, eg, hospital staff); hypoxemia; pulmonary edema (in CREST syndrome patients)
Overdosage/Toxicology: Elevations in methemoglobin and nitrogen dioxide may be signs of overdose. Elevated nitrogen dioxide may cause acute lung injury and elevations of methemoglobin reduce the oxygen delivery capacity of the circulation. NO2 levels >3 ppm or methemoglobin levels >7% were treated by reducing the dose of or discontinuing INOmax�(r). Methemoglobinemia that does not resolve with dosage reduction or discontinuation of therapy may require intravenous vitamin C, intravenous methylene blue, or blood transfusion, depending on the clinical situation.
Drug Interactions: No formal studies have been done. Concurrent use of sodium nitroprusside, nitroglycerin, or prilocaine may result in an increased risk of developing methemoglobinemia. Monitor closely if used. Has been administered with tolazoline, dopamine, dobutamine, steroids, surfactant, and high-frequency ventilation.
Stability: Store at 25°C (77°C)
Mechanism of Action: In neonates with persistent pulmonary hypertension, nitric oxide improves oxygenation. Nitric oxide relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine 3',5'-monophosphate, which leads to vasodilation. When inhaled, pulmonary vasodilation occurs and an increase in the partial pressure of arterial oxygen results. Dilation of pulmonary vessels in well ventilated lung areas redistributes blood flow away from lung areas where ventilation/perfusion ratios are poor.
Pharmacodynamics/Kinetics: Absorption: Systemic after inhalation Metabolism: Nitric oxide combines with hemoglobin that is 60% to 100% oxygenated. Nitric oxide combines with oxyhemoglobin to produce methemoglobin and nitrate. Within the pulmonary system, nitric oxide can combine with oxygen and water to produce nitrogen dioxide and nitrite respectively, which interact with oxyhemoglobin to then produce methemoglobin and nitrate. At 80 ppm the methemoglobin percent is ~5% after 8 hours of administration. Methemoglobin levels >7% were attained only in patients receiving 80 ppm. Excretion: Urine (as nitrate) Clearance: Nitrate: At a rate approaching the glomerular filtration rate
Dosage: Inhalation: Neonates (up to 14 days old): 20 ppm. Treatment should be maintained up to 14 days or until the underlying oxygen desaturation has resolved and the neonate is ready to be weaned from therapy. In the CINRGI trial, patients whose oxygenation improved had their dose reduced to 5 ppm at the end of 4 hours of treatment. Doses above 20 ppm should not be used because of the risk of methemoglobinemia and elevated NO2.
Administration: In the ventilated neonate, precise monitoring of inspired nitric oxide and NO2 should be instituted using a calibrated analysis device with alarms. Sample gas for analysis should be drawn before the Y-piece, proximal to the patient. In addition, oxygen levels should be measured. A backup delivery system should be available in the event of power failure. Do not discontinue abruptly.
Monitoring Parameters: Respiratory status including arterial blood gases with close attention to PaO2, methemoglobin, NO2 , vital signs, blood sugar, signs and symptoms of infection.
Nursing Implications: Monitor oxygenation closely. Improvement will typically occur within 30 minutes of initiation. Do not discontinue therapy abruptly. Additional therapies should be used to maximize oxygen delivery. Monitor for withdrawal reactions (worsening oxygenation, increased PAP) after discontinuation.
Additional Information: Elevations in methemoglobin and nitrogen dioxide may be signs of overdose. Elevated nitrogen dioxide may cause acute lung injury and elevations of methemoglobin reduce the oxygen delivery capacity of the circulation. NO2 levels >3 ppm or methemoglobin levels >7% were treated by reducing the dose of or discontinuing INOmax�(r). Methemoglobinemia that does not resolve with dosage reduction or discontinuation of therapy may require intravenous vitamin C, intravenous methylene blue, or blood transfusion, depending on the clinical situation.
Dental Health: Effects on Dental Treatment: No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions: No information available to require special precautions
Dosage Forms: Gas, for inhalation: 100 ppm [nitric oxide 0.01% and nitrogen 99.9%] (353 L) [delivers 344 L], (1963 L) [delivers 1918 L] 800 ppm [nitric oxide 0.08% and nitrogen 99.92%] (353 L) [delivers 344 L], (1963 L) [delivers 1918 L]
References: American Academy of Pediatrics, Committee on Fetus and Newborn, "Use of Inhaled Nitric Oxide,"Pediatrics, 2000, 106(2 Pt 1):344-5. Davidson D, Barefield ES, Kattwinkel J, et al, "Inhaled Nitric Oxide for the Early Treatment of Persistent Pulmonary Hypertension of the Term Newborn: A Randomized, Double-Masked, Placebo-Controlled, Dose-Response, Multicenter Study: I-NO/PPHN Study Group."Pediatr, 1998, 101(3 Pt 1):325-34. "Inhaled Nitric Oxide in Full-Term and Nearly Full-term Infants With Hypoxic Respiratory Failure." The Neonatal Inhaled Nitric Oxide Study Group, N Engl J Med, 1997, 336(9):597-604.
International Brand Names: INOmax�(r) (CA)
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