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Selective Pulmonary Vasodilator Pregnancy: Limited maternal data — used in peripartum pulmonary hypertension and ARDS; fetal effects unknown; specialist decision required

Nitric Oxide (Inhaled — iNO)

Brand names: INOmax, Noxivent

Adult dose

Dose: ARDS: 5–40 ppm inhaled; Pulmonary hypertension (post-cardiac surgery): 10–40 ppm; Wean by 5 ppm increments every 4 hours
Route: Inhaled via ventilator circuit
Frequency: Continuous inhalation
Max: 80 ppm (rarely used; toxicity risk increases above 40 ppm)
Delivered via calibrated delivery system connected to ventilator. Selective pulmonary vasodilator — dilates ventilated lung segments, improving V/Q matching. Rapidly inactivated by haemoglobin — no systemic hypotension. Used in ARDS (transiently improves oxygenation but no mortality benefit), PPHN (neonates), post-cardiac surgery pulmonary hypertension.

Paediatric dose

Dose: Not weight-based — ppm concentration ppm/kg
Route: Inhaled
Frequency: Continuous
Max: 20 ppm (neonates with PPHN — NICE-approved dose range)
PPHN (persistent pulmonary hypertension of newborn): 20 ppm inhaled — FDA/MHRA licensed for term and near-term neonates (≥34 weeks). INNOVO trial: reduces need for ECMO in PPHN. Reduce by 5 ppm increments when weaning — abrupt cessation causes rebound pulmonary hypertension.

Dose adjustments

Renal

No dose adjustment required — inhaled route, minimal systemic absorption.

Hepatic

No dose adjustment required.

Paediatric weight-based calculator

PPHN (persistent pulmonary hypertension of newborn): 20 ppm inhaled — FDA/MHRA licensed for term and near-term neonates (≥34 weeks). INNOVO trial: reduces need for ECMO in PPHN. Reduce by 5 ppm increments when weaning — abrupt cessation causes rebound pulmonary hypertension.

Clinical pearls

  • ARDS evidence caveat: iNO transiently improves PaO2/FiO2 ratio and reduces pulmonary artery pressure in ARDS, but NO RCT has demonstrated mortality benefit (Cochrane Review 2016); current use is as bridge therapy for severe hypoxaemia (PaO2/FiO2 <100), impending ECMO or as rescue in intractable RV failure
  • PPHN gold standard: iNO at 20 ppm is the definitive treatment for PPHN in term neonates — reduces need for ECMO by 40% (INNOVO trial); remains the only licensed inhaled NO indication in UK for neonates
  • Weaning protocol: NEVER abruptly discontinue iNO — rebound pulmonary vasoconstriction causes acute RV failure; wean 5 ppm every 4–8 hours; co-start sildenafil (0.5 mg/kg oral/NG) as iNO bridge to facilitate weaning
  • Methaemoglobinaemia monitoring: check MetHb within 4 hours of starting and every 8–12 hours; target MetHb <3%; if MetHb >5%, reduce iNO dose; >10%, consider discontinuation and methylene blue antidote
  • ECMO bridge: in refractory ARDS or PPHN not responding to iNO (and prone positioning, high-frequency oscillation in ARDS), escalate to ECMO referral; iNO maintains oxygenation during transfer to ECMO centre

Contraindications

  • Dependent on right-to-left shunt for oxygenation (e.g., severe right ventricular failure with inter-atrial right-to-left shunt — reducing RV afterload may decompress but monitor carefully)
  • Methaemoglobinaemia (>5% baseline)
  • Neonates with left ventricular dysfunction (may worsen pulmonary oedema by increasing pulmonary flow)

Side effects

  • Methaemoglobinaemia (dose-dependent — NO + haemoglobin → MetHb; monitor with co-oximetry)
  • Nitrogen dioxide (NO2) generation (circuit interaction — toxic above 3 ppm NO2; use inline monitoring)
  • Rebound pulmonary hypertension on abrupt withdrawal
  • Platelet inhibition (minor — NO inhibits platelet aggregation)

Interactions

  • Sildenafil/tadalafil (synergistic pulmonary vasodilation — can be used together to wean iNO; additive methaemoglobinaemia risk at high doses)
  • Bosentan/macitentan (combination pulmonary hypertension therapy — used in specialist centres)
  • Haemoglobin-based oxygen carriers (inactivate iNO — theoretical interaction)

Monitoring

  • Continuous pulse co-oximetry (SpO2 and MetHb)
  • Inline NO and NO2 gas analyser (NO2 <3 ppm)
  • Arterial blood gas (PaO2, oxygenation response)
  • Pulmonary artery pressure (PAC or echocardiography)
  • MetHb every 4–12 hours

Reference: BNFc; BNF 90; Cochrane Review: iNO for ARDS (Adhikari et al. 2014); INNOVO Trial (Lancet 2002 — PPHN); MHRA SPC INOmax; ESC/ERS Pulmonary Hypertension Guidelines 2022; Surviving Sepsis Campaign 2021. Verify against your local formulary and the latest BNF before prescribing.

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Curated clinical cross-links plus same-class fallbacks.

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