Nitric Oxide (INOmax)

ED / ICU / Transport

• Neonatal hypoxic respiratory failure with pulmonary hypertension (FDA-labeled): The label covers term and near-term neonates (>34 weeks gestation). The goal is better oxygenation and less need for ECMO. You give it with ventilatory support and other appropriate agents
• PPHN during neonatal transport: the transport team keeps iNO going or starts it in transit, provided they carry a nitric oxide delivery system (see Field & Transport Considerations)

Society guidance: two bodies speak to this. The AHA/ATS 2015 pediatric pulmonary hypertension guideline covers PH treatment in children, and that includes iNO for PPHN. The Canadian Paediatric Society (2023) says yes to iNO in late-preterm and term infants whose hypoxemic respiratory failure persists despite optimal oxygenation and ventilation. Routine iNO in preterm infants on respiratory support? They advise against it.

Other Uses

• Adult ARDS (off-label; not indicated): The label is clear on this one. iNO is not indicated for ARDS. In a 385-patient placebo-controlled trial at 5 ppm, oxygenation rose fast. Days alive and off ventilator support did not budge
• Acute right-ventricular failure or pulmonary hypertension in adults and older children (off-label): ICU and pulmonary hypertension centers use it under protocol. No label covers it. No trial cited on this page backs it. That makes it expert practice
• Prevention of bronchopulmonary dysplasia in preterm infants (not established): four large trials came up short on efficacy. That covers infants at or under 34 weeks

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

• 800 ppm (0.08% nitric oxide in nitrogen): aluminum cylinders, size D (353 L at STP; 344 L delivered) and size 88 (1,963 L at STP; 1,918 L delivered)
• 4,880 ppm: 0.4 L portable cylinder (78 L at STP; 70 L delivered)
• Delivery: only an FDA-cleared, calibrated nitric oxide delivery system (NODS) can deliver it. Its labeling governs setup, training and tech support

Adult Dosing

Pediatric Dosing

Preparation & Administration

• Setup: follow the NODS manual. The label requires a backup battery power supply and an independent reserve NODS for power and system failures
• Dose changes: titrate in ppm. The labeled neonatal ceiling is 20 ppm. The label steers clear of doses above 20 ppm. The CINRGI trial ran 20 ppm for up to 24 hours, then 5 ppm for up to 96 hours. That was trial protocol. It was never a label instruction. NINOS gave 80 ppm to infants who did not fully respond to 20 ppm. At least a partial response happened in 18% on nitric oxide vs 20% on control gas. Bottom line: the 80 ppm step showed no difference from control gas
• Weaning: step down over several stages, never in one jump. Hold several hours at each stage and watch for hypoxemia. Stopping abruptly is the mistake to avoid
• Methemoglobin and NO₂: get a methemoglobin level within 4–8 hours of starting, then keep checking. Track PaO₂ and inspired NO₂ too

Contraindications

• Neonates dependent on right-to-left shunting of blood (labeled contraindication; for example, ductal-dependent circulation)
• There is no other labeled contraindication. Use outside term and near-term neonates is off-label. The label has no information on other age groups.

Precautions

• Left ventricular dysfunction: iNO may raise pulmonary capillary wedge pressure. Watch for pulmonary edema, worse LV function, hypotension, bradycardia and cardiac arrest. Discontinue and give supportive care
• Methemoglobinemia: it rises with dose. Steady state can take 8 hours or more. Nitric oxide donor drugs (prilocaine, sodium nitroprusside, nitroglycerin) raise the risk
• Nitrogen dioxide: NO₂ forms when nitric oxide mixes with oxygen. It can inflame and damage the airway and lung
• Preterm infants (34 weeks or less): BPD prevention efficacy is not established

Hold / Reassess If

• Methemoglobin above 7%: reduce the dose or stop. This is a trial threshold, reported in the label's Overdosage section. The label does not set it as a mandatory stop rule
• NO₂ at 3 ppm or more in the breathing circuit: assess the delivery system per the NODS troubleshooting section, recalibrate the NO₂ analyzer, and adjust the dose or FiO₂
• Hypoxemia, systemic hypotension, bradycardia or falling cardiac output after a stop or interruption: treat as rebound and reinstate immediately
• Pulmonary edema or rising wedge pressure in LV dysfunction: stop iNO and give symptomatic care

Common

• Hypotension: the most common adverse reaction in the label. In CINRGI, it was the only reaction more than 2 percentage points above placebo: 14% on iNO vs 11% on placebo
• Methemoglobin rise: it tracks dose and levels off slowly. Mean levels stayed below 1% at 0, 5 and 20 ppm. At 80 ppm they reached about 5% (see Pharmacology)
• Rebound hypoxemia: it follows an abrupt stop or interruption
• Staff exposure: post-marketing reports describe accidental exposure in hospital staff. The symptoms were chest discomfort, dizziness, dry throat, dyspnea and headache. Keep the room or cabin ventilated and handle exhaust per the NODS manual and agency protocol

Serious / Life-Threatening

Overdose & Toxicity Management

• Excess dose: methemoglobinemia and NO₂ toxicity, which is acute lung injury. Reduce the dose or discontinue nitric oxide
• Persistent methemoglobinemia: IV vitamin C, IV methylene blue or blood transfusion, based on the clinical situation. This page gives no dose for these agents. Follow the institutional protocol
• Lab reference: see the methemoglobin page for levels and other causes of low SpO₂

Clinically Significant Interactions

Nothing to mix. Nitric oxide is inhaled, so it is not mixed with IV drugs. Still, check every drug combination against an institutional compatibility and interaction resource.

• Pediatrics: FDA-labeled only for term and near-term neonates (over 34 weeks). Use the Pediatric Dosing table. Do not extrapolate doses. The Cochrane 2016 review of iNO in ARDS covered adults and children. Its 89 children on iNO and 96 controls showed no significant mortality difference (RR 0.78, 95% CI 0.51 to 1.18).
• Neonates: contraindicated when the neonate depends on right-to-left shunting. For preterm infants (34 weeks or less), BPD prevention is not established.
• Pregnancy: the current DailyMed label text has no pregnancy data. Use in a pregnant patient is a specialist decision. This page gives no recommendation.
• Lactation: the label is silent on lactation.
• Older Adults: the label says nitric oxide is not indicated for the adult population.
• Renal Impairment: no specific adjustment is established. A 2026 adult ARDS meta-analysis found more renal replacement therapy with iNO.
• Hepatic Impairment: no specific adjustment is established. The label does not address hepatic function.
• Obesity / Dosing Weight: not applicable. The dose is a fixed ppm concentration, not a weight-based one.

• Scope: it varies by state and agency protocol. Neonatal and critical-care transport teams run iNO. EMS is not a routine iNO provider.
• Storage & Stability: keep cylinders at 25 °C (77 °F), with excursions between 15–30 °C (59–86 °F). Protect them from shocks, falls, oxidizers, flammables, moisture, and heat or ignition.
• Carried Concentration: cylinders come in 800 ppm (size D and size 88) and 4,880 ppm (0.4 L portable). Read the cylinder label before connecting. You set the dose in ppm on the NODS. Cylinder size does not set it.
• Infusions in Transport: this is not an infusion. Check the NODS, backup battery, reserve NODS and cylinder volume before departure. Cylinder volume and battery life limit the trip.
• Altitude / Environment: MRI is the trap. Use only an MRI-cleared NODS (for example the INOmax DSIR Plus MRI) with MR-conditional size 88 cylinders at 100 gauss or less. Size D and 0.4 L cylinders can become projectiles in the MRI field.
• Staff Exposure & Gas Safety: OSHA occupational limits are 25 ppm for nitric oxide and 5 ppm for NO₂. Ventilate the vehicle. Handle exhaust per the NODS manual and agency protocol.
• Ventilator Circuit: connection to the transport ventilator and NODS integration follow the device manuals. This page does not describe circuit setup.
• Handoff Essentials: ppm dose, start time, last methemoglobin value and time, last NO₂ reading, FiO₂ and PaO₂, delivery system and reserve, cylinder volume left, and any interruption with its length and cause.

Mechanism of Action

• Guanylate cyclase activation: nitric oxide binds the heme of cytosolic guanylate cyclase. That makes more cyclic GMP. More cyclic GMP relaxes vascular smooth muscle
• Selective pulmonary vasodilation: inhaled nitric oxide reaches ventilated alveoli and dilates pulmonary vessels. Hemoglobin scavenges it. So systemic effects are minimal
• Gas exchange: in neonates with PPHN, lower pulmonary vascular resistance and better V/Q matching raise PaO₂
• Chemistry: nitric oxide combines with oxyhemoglobin to form methemoglobin and nitrate. It also combines with oxygen and water to form NO₂ and nitrite

Pharmacokinetics

• Half-life: not labeled. Hemoglobin scavenges nitric oxide efficiently. The effect stays local to ventilated lung
• Metabolism: methemoglobin rose over the first 8 hours. The mean stayed below 1% at 0, 5 and 20 ppm and reached about 5% at 80 ppm. Levels above 7% occurred only at 80 ppm (35% of that group). Median time to peak was 8 hours in 13 neonates in the label's pharmacokinetic data. That fits the label's advice not to exceed 20 ppm
• Elimination: nitrate is the main metabolite excreted in urine. It is more than 70% of the inhaled dose

Generic name

Nitric oxide (inhalation gas)

Brand names (US)

INOmax

Pharmacologic class

Pulmonary vasodilator (inhaled gas)

Therapeutic class

Neonatal pulmonary hypertension and hypoxic respiratory failure therapy

Controlled substance

Not controlled

ISMP high-alert

No: not listed on the ISMP acute-care list as checked (see editorFlags)

Look-alike / sound-alike

None established. Nitric oxide (NO) is distinct from nitrogen dioxide (NO₂) and nitrous oxide (N₂O)

Error-prone abbreviations

"NO" for nitric oxide and "NO₂" or "N₂O": write the full names. Avoid mixing ppm with mcg/kg