pulmonary vasodilator

Inhaled Nitric Oxide

INOmax / Genosyl

Route: inhaled (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)

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

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

All Drugs

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