Inhaled Nitric Oxide
INOmax / Genosyl
pulmonary vasodilatorinhaled (continuous via ventilator circuit)Onset: Minutes (within 5–20 minutes for oxygenation response)Duration: Continuous administration required; rebound occurs within minutes of stopping
Mechanism of Action
Endogenous signaling molecule. Inhaled NO diffuses into pulmonary vascular smooth muscle → activates guanylyl cyclase → increases cGMP → vasodilation. Effect is selective to ventilated lung segments, improving V/Q matching.
Dosing
Adult
ARDS: 5–40 ppm. Start at 5–10 ppm. No benefit above 40 ppm
Neonatal
PPHN: 20 ppm (FDA-approved dose). Wean gradually once oxygenation improves
Indications
- Persistent Pulmonary Hypertension of the Newborn (PPHN)
- Hypoxic respiratory failure in term/near-term neonates
- ARDS (adjunct to improve oxygenation — does not reduce mortality)
- Right heart failure with pulmonary hypertension
Contraindications
- Neonates with congenital heart disease dependent on right-to-left shunting (e.g., hypoplastic left heart, critical pulmonary stenosis with intact IVS)
- Methemoglobinemia (use with caution)
Side Effects
- Methemoglobinemia (most important — dose-dependent)
- Rebound hypoxemia / pulmonary hypertension on abrupt discontinuation
- NO2 formation (toxic byproduct — monitor levels)
- Elevated NO2 levels with high FiO2 (oxidation of NO to NO2)
Monitoring Parameters
- Methemoglobin level (q4h initially, then q8–12h; keep <5%)
- NO2 levels in circuit
- SpO2 and PaO2
- Pulmonary artery pressures / echocardiography
- Rebound hypoxemia on weaning
Drug Interactions
- Sildenafil and PDE-5 inhibitors (additive cGMP — potentiated vasodilation, hypotension)
- Drugs that cause methemoglobinemia (dapsone, prilocaine, nitrates)
Clinical Pearls
- Selective pulmonary vasodilator — does NOT cause systemic hypotension (unlike IV vasodilators)
- FDA-approved only for term and near-term neonates with PPHN
- In ARDS: improves oxygenation short-term but does NOT reduce mortality
- Must NEVER be abruptly discontinued — wean slowly to avoid rebound PPHN
- Methemoglobin forms when NO binds hemoglobin → reduced oxygen-carrying capacity
- Goal in PPHN: improve oxygenation index (OI) < 25; wean when OI < 10
Mnemonic
💡 iNO = I kNOw: Inhaled, No systemic effects, NO abrupt discontinuation
NBRC High-Yield
- Selective pulmonary vasodilator — no systemic hypotension
- PPHN: 20 ppm standard dose
- Monitor methemoglobin (keep <5%)
- ARDS: improves oxygenation but NOT mortality
- Never abruptly stop — rebound pulmonary hypertension
- NO2 toxicity at high FiO2 — monitor circuit NO2 levels