Neonatal iNO Recommendations

Last modified by Sara Kaur on 2022/11/08 06:53

This guideline represents the views of the CAPHC Inhaled Nitric Oxide Collaborative and was arrived at after careful consideration of the available evidence as well as a consensus building process.  The guideline does not override the responsibility of individual clinicians and organizations to make decisions and provide the most appropriate care to infants, children and youth in consultation with the patient and family/guardian.

Download Full PDF of Neonatal Guideline 


  1. An order to initiate iNO should be made by a staff physician, by resident medical staff with staff physician approval, or by a Registered Respiratory Therapist (RRT) under the auspices of a medical directive.  A clear care plan should be articulated including goal/s of therapy, the identification of physiological targets and parameters indicating response to therapy.
  2. iNO will be administered and titrated by the RRT as per staff physician order and/or a medical directive.
  3. Documentation to explain reasons for deviation from the guideline are recommended for the purposes of providing new evidence to inform future guidelines.


  1. Neonates with hypoxemic respiratory failure associated with clinical or echocardiographic evidence of pulmonary arterial hypertension

Inclusion Criteria

Persistent hypoxemic respiratory failure secondary to pulmonary hypertension despite measures to ensure adequacy of lung expansion (including evaluation by CXR and use of exogenous surfactant and/or high-frequency modes of ventilation, when appropriate) and correction of acidosis (pH < 7.25)

Patients will meet one or more of the following criteria:

  1. Oxygenation Index of 15-25 or higher
  2. Pre- and post-ductal saturation difference of ≥ 20%
  3. Post-ductal PaO2 < 60 mm Hg with FiO2 of > 0.6
  4. Post-ductal SaO2 < 92% with FiO2 of 1.0



  1. Known or suspected congenital heart disease with increased pulmonary venous pressure or where systemic perfusion is dependent upon extrapulmonary right-to-left shunting. 

Relative contraindications:

  1. Known or suspected severe intraventricular hemorrhage (IVH).
  2. Active pulmonary or gastrointestinal hemorrhage.

Cautions or considerations:

  1. Caution in infants < 28 weeks’ gestation during the first 3 days of life (due to high risk for IVH).  Cranial ultrasound should ideally be performed prior to initiation.
  2. Caution in patients with bleeding tendency (e.g., thrombocytopenia) and/or coagulopathy/DIC.  Consider correction with blood products prior to initiation.
  3. Literature does not support prolonged use in chronic pulmonary hypertension or in right ventricular dysfunction in the absence of associated pulmonary hypertension.

Equipment and Procedure

It is recommended that Health Canada-approved INO delivery systems should be used to assure consistent and safe gas delivery and monitoring during therapy. 

Staff operating such equipment should have evidence of education, training and competencies.

Monitoring & Documentation

Document: (frequency as per local NICU protocol)

  1. Vital signs: Blood pressure, heart rate, pre- and post-ductal SaO2, FiO2
  2. Respiratory status: pulmonary ausculatation, work of breathing, ventilator parameters and endotracheal tube placement
  3. Post-ductal arterial blood gas and calculation of Oxygenation Index (recommended, but not mandatory) 

Prior to Administration of iNO

  1. Echocardiographic confirmation of PPHN is desirable but not mandatory
  2. Optimize lung inflation (using maneuvers as suggested under inclusion criteria)
  3. Correct acidosis
  4. Optimize sedation
  5. Optimize cardiac output (consider volume loading and/or inotropes)

Starting Dose

  1. 20 ppm is the recommended starting dose (doses > 40 ppm have greater potential to cause toxicity without evidence of incremental or additional benefit)
  2. Evaluation of response time should be 30 – 60 minutes
  3. Avoid other changes during the evaluation period as much as possible.

Assessment of Response

Complete, partial or no response based on changes in Fi02, SaO2, and PaO2

Complete Response
Increase in PaO2  > 20 mmHg or SaO2 > 10% or reduction in FiO2 by greater than 0.2
 Partial Response

Increase in PaO2 by 10-20 mmHg or SaO2 5-10 % or reduction in Fi02 by 0.05-0.1

 No Response 

Increase in PaO2 < 10 mmHg or SaO2 < 5 % or change in FiO2 by < 0.05

In the event of no response, iNO can be safely discontinued abruptly within 1 hour of initiation.  In non-responders treated with iNO for > 1 hour, follow the weaning protocol (below) without reference to FiO2.


  1. A review of iNO weaning criteria and patient readiness for weaning should be discussed as part of the patient care plan (daily as a minimum).
  2. Weaning of iNO should commence as soon as criteria are met and patient readiness is established.
  3. When iNO is being weaned, every effort should be made to minimize changes to other treatments. 
  4. The minimum time between initiation of iNO and initial wean should be 2-6 hours.
  5. Consider weaning when patient is stable and Fi02 is < 0.4-0.6


  1. Wean from 20 to 10 ppm.
  2. Within 1- 2 hours, if no deterioration occurs, wean to 5 ppm.
  3. Then, wean iNO in increments of 1 ppm every 1-2 hours until discontinuation.
  4. Prior to discontinuing iNO, consider temporarily increasing FiO2 by 0.1-0.2 for 10 min (pre-oxygenation).

Monitoring for Complications


Measurement of methemoglobin level is highly recommended, ideally within 1 - 2 hours of initiation, then minimum daily or as determined by the medical team.

Methemoglobin level  Action 
 Greater than 10%  Wean as quickly as possible to OFF
  5% to 10 % Wean to 50% of current dose and repeat level within 1-2 hours, consider early and rapid weaning
  2.5% to 5% Consider early weaning

Monitoring of Nitrogen Dioxide (NO2)

Continuous NO2 monitoring should be routine practice.

Consistent Nitrogen Dioxide Level




NO2 < 2 ppm


NO2 >2 ppm

Wean iNO (and FiO2) as quickly as possible

Rebound Pulmonary Hypertension

Definition: Absolute increase in Fi02 requirement of > 0.2  


Return to previous iNO dose for minimum 4 hours before reinitiating weaning then, wean by 1 ppm every 1-2 hours until OFF.  

Consider pre-oxygenation prior to weaning from 1 ppm to OFF, as described above.

Download Full PDF of Neonatal Guideline

Created by Lisa Stromquist on 2015/09/25 23:04

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