Inhaled Nitric Oxide
A study on the effects of inhaled
Nitric Oxide (iNO) in neonatal
Pulmonary Hypertension
by:
 Cecilia Cherian
 Marc Chiappetta
 Jay Suerte
 Santos Machoka
Biological Question
 Is
the administration of low dose versus
high dose nitric oxide effective in the
treatment of persistent pulmonary
hypertension of newborn ?
Hypothesis
 Administering
low dose inhaled nitric oxide
improves oxygen delivery and compliance,
thus is beneficial in treating persistent
pulmonary hypertension of newborns.
What is Nitric Oxide ?
 Nitric
Oxide is a highly diffusible, lipid
soluble free radical that oxidizes quickly to
nitrogen dioxide (NO2) in the presence of
oxygen
 It is produced internally in every cell and
organ in the human body.
How iNO works
 iNO
is a selective pulmonary vasodilator.
 iNO will dilate only the pulmonary blood
vessels adjacent to functioning alveoli.
 iNO diffuse into the capillaries, free NO
immediately binds to hemoglobin forming
nitrosylhemoglobin, which is rapidly
oxidized to methmoglobin and eventually
undergoes conversion to reduced the
hemoglobin
Indications for iNO

iNO is used to treat pulmonary hypertension
such as primary pulmonary hypertenison(PPH)
and persistent pulmonary hypertension of
newborns (PPHN).
 Neonates with hypoxic respiratory failure
associated pulmonary hypertension.
 NO therapy is often used with other forms of
therapy including high frequency oscillatory
ventilation and surfactant therapy, both of which
are aimed at improving oxygen delivery and lung
compliance.
Dosage
 Initial
dosage was 20 ppm(particles per
million).
 Often
reduced to 5 ppm at the end of 4
hours of initial treatment.
 Reduce
inhaled nitric oxide dose by 50%
(20, 10,5, 1 ppm).
Methods of administration
 NO
is delivered with the O2 at a constant
concentration throughout the breathing
cycle.
 Set NO level is stable over a wide range of
flows and flow patterns, including
spontaneous breathing modes.
 The flow sensor placed in the outlet of the
ventilator upstream from the humidifier
measures minute ventilation (lpm).
Method of administration

The injector varied the nitric oxide based on the
measured ventilation.
 Nitric oxide, nitrogen dioxide and oxygen are
measured in the inspiratory limb of the circuit,
just before the patient wye and a calibration
mode verified proper analyzer function. High
and low alarms are provided for all three gases
and an automatic cut-off to prevent nitric oxide
overdose.
Hazards and contraindications

Nitric oxide when combined with oxygen
produces nitrogen dioxide (NO2), which is a
toxic gas.
 Because of it’s very minimal half life (0.1
seconds – 5 seconds), it is quickly inactivated
once it combines with hemoglobin.
 Although rare, the patients as well as health care
providers can be adversely affected.
 Factors influencing NO2 production are O2
concentration, NO concentration and time of
contact between NO and O2.
Hazards and contraindications

Patients most at risk include those receiving high
oxygen concentration and low ventilator flow
rates.
 Production of methemoglobin can be a problem
due to anemic hypoxia which can be treated with
vitamin C..
 A major contraindications of this therapy is
children who as a result of congenital cardiac
anomalies need a right-to-left shunt to survive
and NO therapy corrects the right-to-left shunts.
methodology

A patient group of 34 weeks gestation to 8 days
old were selected for the iNO treatment.
 All these patients had persistent pulmonary
hypertension and severe respiratory failure
requiring mechanical ventilation.
 Infants that were diagnosed with pneumonia,
sepsis, and meconium aspiration were included.
 Infants diagnosed with congestive heart defect
(CHD) were excluded because previous studies
showed that these infants did not respond to iNO
therapy.
methodology

Data collection
 After parental consent was obtained, eligible patients
with 2 separate Oxygen Indices (OIs) of >10 were
randomized to receive a starting iNO dose of either 1 to
2 ppm (low dose group) or 10 to 20 (high dose group).
 In the high dose group the therapy was started at 20
ppm and could be decreased to 5 ppm in the first 24
hours.
 In the low dose group starting at 1 ppm and not obtaining
a positive result, increasing the ppm in small increments
were made until desired results were obtained.
(increased oxygen index)
methodology
 Data
collection
 The response of iNO dose was assessed
according to the increase in arterial PaO2
and decrease in OI 30 to 60 minutes after
exposure to initial starting concentration.
 After the first 24 hrs. they had to be
weaned to 5 ppm for no more than 96
hours.
methodology
 Data
collection
 Failure to improve after 96 hours were
considered for ECMO therapy.
 All discontinuation of therapy was
performed at doses of 0.5 to 1 ppm.
 When any response occurred to 40 ppm or
greater, attempts were made every 4
hours to halve the dose, until the infant
was receiving 20 ppm.
methodology
 Data
collection
 During the treatment period no changes
were made to ventilator or any other
therapies.
 Methemoglobin analysis was performed
before iNO administration and at 6 hours
and every 8 hours during iNO
administration.
Statistics
 An
objective discussion of the three
research papers clinical findings indicated
the validity of inhaled nitric oxide on the
neonatal population.
In the neonatal population that
ended up needing ECMO

Of the group that initially had nitric oxide
therapy 47% of them did survive the hospital
stay, while only 36 % of the control group
survived (where N= 248+38=286 patients)
 These patient population was identical in
gestation (mean 35 wks old), age (mean 2.5
days old), the control group started with an initial
treatment of 0ppm iNO, and an oxygenation
index of >25.
Conclusion
 While
one paper proves objectively that
starting patients at low doses of nitric
oxide can have an inhibiting effect on
future increments of nitric oxide therapy all
the papers agree that nitric oxide therapy
is more useful than 100 % oxygen in the
treatment of PPHN secondary to
pulmonary hypoxia.
Conclusion
 Gradually
weaning of the nitric oxide to an
acceptable dose is carefully monitored by
using different criteria including but not
limited to oxygen indices and ABGs.
 Nitric oxide is used in conjunction with
oscillator therapy.
Conclusion
 Nitric
Oxide is used as a precursor to
ECMO therapy which is more expensive
and has more risk factors.
Glossary

1. Persistent Pulmonary Hypertension of Newborn
(PPHN)- A syndrome that causes right to left shunt,
severe hypoxemia, and mixed acidosis.

2. Parts Per Million (ppm)- Unit of measurement used
for nitric oxide.

3. Nitric Oxide (NO)- A selective pulmonary vasodilator
that improves blood flow to ventilated alveoli, resulting
decreased shunt and improve oxygenation.
Glossary

4. Nitrogen Dioxide (NO2)- A toxic gas
produced when nitric oxide is combined with
oxygen.

5. Methemoglobin (metHb)- The result when
Nitric Oxide combines with Hemoglobin,
resulting in oxygen desaturations.

6. Hemoglobin (Hb)- Oxygen carrying protein
found in the blood that carries oxygen from the
lungs to the cells.
Reference

1. Clark, R.H., Kueser, T.J., & Walker, M.W. Low-Dose Nitric Oxide
Therapy for Persistent Pulmonary Hypertension of the Newborn. The
New England Journal of Medicine. (Feb. 17, 2000). Retrieved from:
http://content.nejm.org/cgi/content/full/342/7/469?ijkey=a3f529d65be4b34d2
f21ab8cb3b.

2. Finer, N.N., Sun, J.W., Rich, W. Randomized, Prospective Study of
Low Dose Versus High Dose Inhaled Nitric Oxide in the Neonate with
Hypoxic Respiratory Failure. Journal of the Academy of Pediatrics. (Oct.
2001). Retrieved from:
http://pediatrics.aappublications.org/cgi/content/full/108/4/949.

3. Cornfield, D.N., Maynard, R.C., & Deregnier, R. Randomized ,
Controlled Trial of Low Dose Inhaled Nitric Oxide in the Treatment of
Term and Near Term Infants with Respiratory Failure and Pulmonary
Hypertension. Official Journal of the American Academy of Pediatrics.
(Nov. 1999). Retrieved from:
http://pediatrics.aappublications.org/cgi/content/full/105/5/1089
Extra links
 How
to set up a nitric oxide system
El fin