• Persistent pulmonary hypertension of the newborn in term and near term (>34 weeks) babies, proven on clinical grounds or by echocardiography [see Persistent pulmonary hypertension of the newborn (PPHN) guideline]
• Oxygen index >20
• Pre and post ductal SpO² difference >10%
• Initiate treatment with nitric oxide (NO) only after discussion with on-call consultant
• Babies requiring NO should be referred to a NICU for ongoing management, in accordance with Toolkit principles 

• Preterm baby
  
  • no evidence of benefit for preterm babies needing ventilation for RDS and some evidence of harm 
  • may be some survival benefit for preterm babies with pulmonary hypoplasia and PPHN – discuss with consultant  
• Platelets <50 x 10⁹/L
• Known or suspected major haemorrhage 
• Congenital diaphragmatic hernia

• Congenital heart disease (especially circulations dependent on right-to-left shunting)

Starting NO

Preparation

• Ensure ventilation optimal and that other aspects of the Persistent pulmonary hypertension of the newborn (PPHN) guideline have been followed
• Echocardiogram (if available) to exclude cyanotic congenital heart disease 
• A sustained inflation immediately before starting NO can enhance response

Administration

• Document FiO₂ and SpO₂ immediately before starting NO
• Start NO at 20 ppm
• NO displaces oxygen so expect inspired oxygen displayed on INOvent to read lower than that on ventilator. Ensure consistency of documentation on charts
• Assess response after 30–60 min. If no response (see below) stop NO
• NO can be stopped abruptly without weaning if given for <4 hr

Definition of responses to NO

• An increase in SpO₂ or PaO₂ whilst on the same ventilator settings or an ability to wean FiO₂ whilst maintaining SpO₂ occurring within 60 min of starting NO
• Approximately 30% of babies with PPHN do not respond to NO

Table 1: Definition of a response to NO

Weaning

• If no response to NO after 60 min stop NO without weaning 

• If NO has been administered for ≥4 hr, wean gradually to prevent rebound (as below)

• If full or partial response to NO when preductal SpO₂ can be maintained in target range with FiO₂ <0.6 and after at least 4 hr treatment weaning can be attempted 

  • reduce NO to 10 ppm

  • in 1–2 hr reduce NO to 5 ppm

  • in 1–2 hr reduce NO to 4 ppm and continue to reduce NO by 1 ppm every 1–2 hr

  • after 1–2 hr at 1 ppm increase FiO₂ by 0.1–0.2 10 min before stopping NO 

  • some babies will require low dose (<0.5 ppm) for some time (up to 24 hr) during weaning

    • may be necessary to temporarily increase FiO₂ by 0.1–0.2 to facilitate weaning 

• Failure of weaning is defined as either

  • >5% reduction in SpO₂ or

  • need to increase FiO₂ by >0.2 to maintain SpO₂ or

  • development of >10% difference between pre- and postductal SpO₂

• If weaning fails at any stage increase NO to previous dose and wait ≥4 hr before trying again 

• Once discontinued, wait ≥6 hr before removing NO circuit from ventilator

   

• Use SpO₂ to monitor response 
• Blood gases 4-hrly 
• Monitor methaemoglobin before starting NO, 1 hr after starting and then 12-hrly. Maximum proportion of total haemoglobin is reached after 8 hr
  
  • normal <1%
  • 2–3% is acceptable
  • 4% requires action: reduce NO and repeat in 1 hr
    
    • if still >4%, stop NO
    • if >6%, treat with methylthioninium chloride (methylene blue) 1 mg/kg IV over 1 hr
• NO inhibits platelet function and can trigger bleeding if baby has bleeding problem or thrombocytopenia. Check FBC daily while baby receiving NO
• If NO₂ >1 ppm reduce NO dose