RSPT 2353 – Neonatal/Pediatric Cardiopulmonary Care
Inhaled Nitric Oxide (iNO)
Lecture Notes
Reference: INOTherapeutics Speaker’s Bureau
I. Indications –
a. Hypoxic Respiratory Failure –
A relative deficiency of oxygen in arterial blood and insufficient minute
ventilation as evidenced by respiratory acidosis requiring intubation and
mechanical ventilation
b. Hypoxemia –
 Severity is indicated as oxygen index
FiO2 X MAP
OI =
X100
PaO2
 A sustained OI of >25 is an indication for iNO and/or HFOV
 A sustained OI of >40 is an indication for ECMO
c. Persistent Pulmonary Hypertension of the Newborn
 Can be related to underlying lung disease
 Idiopathic
 Any pathology that can cause intrapulmonary or extrapulmonary
shunting.
d. Cardiopulmonary Interactions in PPHN
 Relationship of lung disease to pulmonary hypertension
1. PVR ↑ at lung volumes above and below FRC
a. Underinflation – RDS
b. Overinflation – MAS
2. Extremes of lung volume contribute to high PVR and
extrapulmonary shunting
 Relationship of Cardiac Dysfunction to Pulmonary hyptertension
1. LV dysfunction causes ↑ L atrial pressure & pulmonary
venous hypertension
2. May affect RV-dependant systemic circulation - ↑
pulmonary blood flow doesn’t improve systemic circulation
3. Pt with extremely low LV ejection fraction may develop
pulmonary edema
II. Treatment
a. AAP Recommendations
 Infants with progressive HRF should be cared for in centers able to
provide multiple modes of ventilatory support and rescue therapies
or be transferred to such an institution
 An echocardiogram to rule out congenital heart disease is
recommended; center-specific criteria for treatment failure should
be developed to facilitate timely consideration of alternative
therapies
 If iNO is offered by a center without ECMO capability, treatment
failure criteria and mechanisms for timely transfer of infants to an
b.
c.
d.
e.
f.
ECMO center without interruption of iNO therapy should be
established prospectively
 Centers that provide iNO therapy should provide comprehensive
long-term medical and neurodevelopmental follow-up
 Centers that provide iNO therapy should establish prospective data
collection for treatment time course, toxic effects, treatment failure,
use of alternative therapies, and outcomes
Indications & Contraindications
 Indications
1. Term and near-term (>34 weeks) newborns with HRF
2. Clinical or echocardiographic evidence of adequate LV
performance and extrapulmonary right-to-left shunting
3. Newborns treated with ventilatory support and appropriate
adjunct therapies
 Contraindications
1. Neonates with severe LV failure who may have
RV-dependent systemic circulation
2. Neonates with congenital heart disease that depends on a
right-to-left shunt at the ductus arteriosus may deteriorate
with iNO
3. Neonates with undiagnosed pulmonary venous obstruction
may have transient improvement with iNO followed by
deterioration
Echocardiography – If time allows echocardiography should be performed
 Define anatomy (rule out cyanotic heart disease, HLHS)
 Demonstrate presence of PPHN and extrapulmonary right-to-left
shunting
 Characterize cardiac performance
 Rule out right-to-left ductal dependence (LV failure)
Dosage
 20 ppm
 Higher doses are not proven to be more effective in improving
oxygenation and are associated with adverse events
 Recommendation is use of iNO up to 14 days
Weaning
 Should be gradual; Use caution when weaning from or
discontinuing iNO
1. Abrupt discontinuation may cause
a. Increase in PAP
b. Worsening of PaO2
iNO Toxicity
 Prolonged exposure to high doses of iNO (>40 ppm) causes toxicity
1. Methemoglobinemia (>5%)
2. Increase in delivered NO2
 Adverse effects due to high doses of iNO should initially be treated
by reducing iNO dose
 Specific therapy for methemoglobinemia may include
1. PRBC transfusion (in presence of anemia)
2. Ascorbic acid (vitamin C)
 Therapy with methylene blue should be avoided except in extreme
cases
g. iNO Delivery
III. Environmental Factors
a. Monitor environmental levels of NO/NO2
b. Scavenging of NO/NO2 from ventilator exhaust
c. Minimize exposure to staff and patients to NO/NO2
 Optimizing the lowest dose for the pt minimizes the risk to the
healthcare worker