nitric oxide gas (Rx)

>10%

Hypotension (13%)

Withdrawal (12%)

1-10%

Atelectasis (9%)

Hematuria (8%)

Hyperglycemia (8%)

Sepsis (7%)

Infection (6%)

Cellulitis (5%)

Stridor (5%)

Frequency Not Defined

Intracranial hemorrhage, due to platelet aggregation inhibition

Seizure

Gastrointestinal hemorrhage due to platelet aggregation inhibition

Methemoglobinemia

Hematuria due to platelet aggregation inhibition

Acute lung injury, atelectasis, hypoxemia, pulmonary edema, pulmonary hemorrhage, pulmonary toxicity due to nitrogen dioxide formation

Postmarketing Reports

Accidental exposure to nitric oxide for inhalation in hospital staff has been associated with chest discomfort, dizziness, dry throat, dyspnea, and headache

Contraindications

Hypersensitivity

Neonates dependent on right-to-left shunting of blood

Cautions

Methemoglobinemia and NO2 levels are dose dependent; the most common adverse reaction is hypotension

Closely monitor PaO2 and methemoglobin levels; measure methemoglobin levels within 4-8 hr after initiation of treatment and then periodically throughout treatment

Monitor NO2 levels continuously with a suitable nitric oxide delivery system

If methemoglobin levels are elevated and do not resolve with decreased dose or discontinuation, additional therapy may be warranted (eg, IV vitamin C, IV methylene blue, blood transfusion); hypoxemia from methemoglobinemia may occur

Wean gradually to avoid rebound pulmonary hypertension syndrome; symptoms include worsening oxygenation, increased pulmonary artery pressure (PAP), systemic hypotension, and decreased cardiac output; reinstate nitric oxide immediately

Nitrogen dioxide (NO2) forms in gas mixtures containing NO and O2 and may cause airway inflammation and damage to lung tissues; if NO2 exceeds 0.5 ppm, decrease the dose of nitric oxide

If there is unexpected change in NO2 concentration, or if NO2 concentration reaches 3 ppm when measured in breathing circuit, assess delivery system; may need to adjust dose as appropriate

Patients with left ventricular dysfunction may experience pulmonary edema when treated with nitric oxide, increased pulmonary capillary wedge pressure, worsening of left ventricular dysfunction, systemic hypotension, bradycardia, and cardiac arrest

Drug interaction overview

• Nitric oxide donor agents such as prilocaine, sodium nitroprusside and nitroglycerine may increase risk of developing methemoglobinemia

Pregnancy

Limited data available; risk of adverse outcomes increased in pregnant patients with pulmonary arterial hypertension; inhaled nitric oxide may be used to improve pulmonary blood flow and oxygenation in pregnant patients with pulmonary hypertension who also have cardiac decompensation

Lactation

Nitric oxide and metabolites are endogenous to breast milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Relaxes vascular smooth muscle, resulting in pulmonary vasodilation

Combines with oxyhemoglobin to produce methemoglobin & nitrate

Excretion

Nitrate excreted quickly, renal

Ventilator Administration

Validated ventilatory systems

• Must be adminstered using a calibrated and validated nitric oxide delivery system by trained personnel for the particular brand (eg, INOmax, Genosyl)
• Keep available a back up battery power supply and an independent reserve nitric oxide delivery system to address power and system failures

• INOmax

  • Consult the delivery system label or call 877-566-9466 or visit inomax.com for a current list of validated systems

• Genosyl

  • Consult the Delivery system operator’s manual or call 1-877-337-4118 or visit www.vero-biotech.com

Monitoring

• Measure methemoglobin within 4-8 hr after initiating and periodically throughout treatment
• Monitor for PaO2 and inspired NO2 during administration

Weaning and discontinuation

• Avoid abrupt discontinuation; wean gradually
• To wean, downtitrate in several steps, pausing several hours at each step to monitor for hypoxemia