All you need to know about Pulmonary hypertension (PPHN) of newborn

1. Persistent Pulmonary
Hypertension
(PPHN/PFC)
of the Newborn
Dr.Sid Kaithakkoden MD
MBBS,DCH,DNB,MD,MRCPCH,FCPS
alavisaid@aol.com

2. PPHN/PFC
• Disorder of the transitional circulation wherein
unsaturated blood continues to bypass the lungs
by way of the foramen ovale and/or the ductus
arteriosus
• PPHN is the failure of PVR to fall at birth
• The transition from fetal circulation to extra uterine
circulation is not complete
• R-L shunting occurs through a patent ductus
arteriosus and foramen ovale
• Infants remain cyanotic after birth ( similar to
those with cyanotic CHD)

3. Typically seen in:
• Full term or post term infants
• 37-41 weeks gestational age
• within the first 12-24 hours after birth

4. PPHN
• Primary
– Normal cardiac anatomy, normal labs except
for cyanosis
• Secondary
– Meconium aspiration syndrome
– Asphyxia
– Sepsis (GBS, E. coli, etc)
– Congenital diaphragmatic hernia
– Congenital heart disease (rarely)
– Others

5. Primary PPHN
• Classical PPHN
– idiopathic
– Hypoxemia develops in a baby with normal
lungs
– Breath sounds and CXR are usually normal

6. Possible causes
• Chronic intrauterine hypoxia
• Asphyxia
• Maternal ingestion of prostaglandin
– Premature ductal closure
– Mothers who took aspirin near term caused repeated
intrauterine closure of the ductus with redirection of
blood into the pulmonary vasculature
• Hypoglycemia
• Hypothermia
• Maternal hypertension

7. Secondary PPHN
• PPHN secondary to lung disease
– meconium aspiration syndrome
– congenital diaphragmatic hernia
– group B streptococcal pneumonia
– respiratory distress syndrome
– sepsis
– lung hypoplasia

10. Fetal Shunts
• Ductus arteriosus
– R-L shunting of blood from pulmonary artery to
the aorta bypasses the lungs
– Usually begins to close 24-36 hours after birth
• Foramen ovale
– Opening between left and right atria
– Closes when there is an increased volume of
blood in the left atrium

11. Ductus Arteriosus
• Blood pumped from
the right ventricle
enters the pulmonary
trunk
• Most of this blood is
shunted into the aortic
arch through the
ductus arteriosus

12. Foramen Ovale
• Blood is shunted from
right atrium to left atrium,
skipping the lungs
• More than one-third of
blood takes this route
• Is a valve with two flaps
that prevent back-flow

13. What happens at birth?
• The change from fetal to postnatal circulation happens
very quickly
• Changes are initiated by baby’s first breath

14. What Happens at Birth? (contd)
• With the first breaths of life, fetal lung fluid is
cleared, FRC is established, surfactant is
secreted
• Coincident with cord clamping, the low resistance
placenta is removed and systemic resistance
rises
• A rise in pO2 causes a fall in PVR, resulting in
increased PBF
• Increased pulmonary venous return to the LA
increases LA pressure, functionally closing the FO
• The increase in PBF, as well as the increase in
pO2, decreases ductal level shunting

15. Foramen ovale Closes shortly after birth,
fuses completely in first
year
Ductus arteriosus Closes soon after birth,
becomes ligamentum
arteriousum in about 3
months
Ductus venosus Ligamentum venosum
Umbilical arteries Medial umbilical ligaments
Umbilical vein Ligamentum teres

16. Normal Pulmonary Vascular
Transition
• The pulmonary vascular transition at birth
is characterized by :
– rapid increase in pulmonary blood flow
– reduction in PVR
– clearance of lung liquid

17. PPHN
• Failure to achieve the normal decrease in PVR at
birth
• Altered pulmonary vascular tone, reactivity and/or
structure
• Severe hypoxemia as a result of right-to-left
shunting of blood across the DA and FO
• Common condition among infants requiring
neonatal intensive care
– 1-2 per 1000 live births
– 10-20% mortality

18. Signs of PPHN
• Infants with PPHN are born with Apgar
scores of 5 or less at 1 and 5 minutes
• Cyanosis may be present at birth or
progressively worsen within the first 12-24
hours

19. Later developments
• Within a few hours after birth
– tachypnoea
– retractions
– systolic murmur
– mixed acidosis, hypoxemia, hypercapnia
• CXR
– mild to moderate cardiomegaly
– decreased pulmonary vasculature

20. Pulmonary Vasculature
• Pulmonary vascular bed of newborn is
extremely sensitive to changes in O2 and
CO2
• Pulmonary arteries appear thick walled
and fail to relax normally when exposed to
vasodilators
• Capillaries begin to build protective muscle
(remodeling)

21. Assessment of Infant with PPHN
• Airway Patency
• Alveolar Recruitment
• Underlying Pulmonary Vascular
pathology
• Degree and level of shunt
• Myocardial
– Filling volumes
– Contractility
– Structural abnormalities

22. PPHN
• Diagnosis
– Hypoxemia poorly responsive to O2
– ‘Differential cyanosis’
• Rt.radial - descending aorta diff. 1.33kPa or 5%

23. Diagnosis
Hyperoxia Test
• Place infant on 100% oxyhood for 10
minutes.
– PaO2 > 100 mmHg parenchymal lung
disease
– PaO2= 50-100 mmHg parenchymal lung
disease or cardiovascular disease
– PaO2 < 50 mmHg fixed R-L shunt cyanotic
congenital heart disease or PPHN

24. Hyperoxia Test (cont.)
• If fixed R-L shunt
– need to get a preductal and postductal arterial
blood gases with infant on 100% O2
• Preductal- R radial or temporal artery
• Postductal- umbilical artery
– If > 15 mmHg difference in PaO2 then ductal
shunting
– If < 15 mmHg difference in PaO2 then no ductal
shunting

25. Echocardiography
• PFO / PDA patent / RV strain / bulging
intraventricular septum
• R → L (or bidirectional) shunt across PDA/
• R ventricle may be larger than normal
• increased pulmonary artery pressure
• increased pulmonary vascular resistance

27. Treatment Goals:
• Maintain adequate oxygenation
– These babies are extremely sensitive
– Handling them can cause a decrease in PaO2
and hypoxia
– Crying also causes a decrease in PaO2
– Try to coordinate care as much as possible
• Maintain neutral thermal environment to
minimize oxygen consumption

28. Management (contd)
• Supportive
• Avoid hypothermia, hypoglycaemia,
hypovolaemia, hypocalcaemia, anaemia
• Correct metabolic acidosis
• Treat underlying cause (e.g. sepsis)
• ↑systemic arterial BP → ↓L to R shunt

29. Management (contd)
• Provide oxygen and ventilate
• Sedate and paralyze
• Vasodilator drugs
• High frequency ventilation
• Inhaled nitric oxide
• ECMO

30. Vasodilator drugs
• Tolazoline
• Prostacyclin
• Sodium nitroprusside
• Verapamil
• Nifedipine
• Magnesium sulphate
• Sildenafil
• Adenosine

31. Tolazine
– Pulmonary and systemic vasodilator
– pulmonary response needs to assessed by
giving 1-2 mg/kg through peripheral vein
• if positive response- start continuous infusion of 0.5-
1.0 mg/kg/hr
– Monitor closely for GI bleeding, pulmonary
hemorrhage and systemic hypotension
– May need to also give Dopamine or
Dobutamine to maintain systemic blood
pressure and to increase CO

32. Management (contd)
Respiratory
• Avoid high PVR due to high or low lung volumes
• Minimise risk of lung injury
• Some may respond to:
– V.high lung volume strategy on HFOV
– ‘open lung’ approach (high PEEP, low tidal volume)
– Surfactant
• Avoid hyperventilation
– Increases risk of VILI
– Response to alkalosis likely to be transient
– Increased risk of adverse neurodevelopmental outcome
due to ↓cerebral blood flow

33. HFOV
• High frequency oscillatory ventilation
– decrease risk of barotrauma
– effective alveolar ventilation
– alveolar recruitment
• Nitric Oxide more effective
• HFOV more effective in PPHN babies with
lung disease

34. 5-20ppm improves oxygenation
and reduces the need for ECMO
in PPHN
Inhaled nitric oxide
(iNO)

36. • cGMP is a second messenger of nitric
oxide (NO)
• Stabilization of cGMP results in increasing
nitric oxide (NO) at the tissue level leading
to pulmonary vessel vasodilatation
• Nitric oxide has been considered the
closest thing to an ideal vasodilator

38. Nitric oxide (NO) and prostacyclin (PG) signaling pathways in regulation of
vascular tone

39. Recommendations for the
use of iNO
• Who to Rx:
– Near term (>34 weeks) and term NB with OI>25, and
echocardiographic evidence of adequate CO and R L shunt
• Starting dose:
– 20 ppm; Maximum dose: 20 ppm; Reduce to 5 ppm in first 4-24 h
• Duration:
– < 5 days in most cases; exception – CDH
• Weaning:
– Decrease to 5 ppm in first 4-24 h; Decrease by 1 ppm to 1 ppm
before discontinuing
• Discontinue:
– When FiO2 < 0.6 and PaO2 >60 for 30-60 min on 1ppm; Increase
FiO2 by 10-15% before discontinuing iNO; Observe for rebound

40. Subtleties of iNO Use
• Rebound can occur, even in non-responders
– This has implication for use of NO in non-ECMO centers
and for transport
• Poor lung inflation with inadequate alveolar
recruitment is the most common cause of
treatment failure
– HFOV combined with iNO resulted in less ECMO use
compared with either Rx alone
– Surfactant decreased the use of ECMO in RDS, MAS,
and sepsis, but not idiopathic PPHN

41. iNO and PPHN: Summary
• iNO reduces use of ECMO without influencing
LOS, ventilator days, long-term
neurodevelopmental outcomes or mortality
• iNO is not efficacious in all infants with PPHN
– 40% non-responders
– Infants with CDH represent a therapeutic challenge
• Infants with parenchymal lung disease most likely
to respond to combined therapy with iNO plus a
lung volume recruitment strategy, such as HFOV,
optimal PEEP, or surfactant therapy

42. iNO in the Premature Lung
• iNO improves gas exchange, decreases PVR,
decreases lung neutrophil accumulation in the
mechanically ventilated premature lamb with RDS
(Kinsella et al, 1994, 1997)
• In the premature baboon, iNO improves early
pulmonary function and favorably alters
extracellular matrix deposition
(McCurnin et al, 2005)
• iNO enhances distal lung growth in newborn
animals exposed to hyperoxia (Lin et al, 2005) and
mechanical ventilation (Bland et al, 2005)

43. Potential risks of iNO in the
Premature Newborn
• Prolongation of bleeding time (dose
dependent) with attendant risk of
intracranial hemorrhage
• Decreasing pulmonary vascular
resistance in presence of PDA could
lead to pulmonary overflow, edema,
hemorrhage
• Potential effects on surfactant
function

44. Poor response to iNO
• Inadequate lung inflation
• Severe pulmonary hypoplasia
• Poor myocardial function / low
systemic BP
• Wrong diagnosis

45. Summary and
Conclusions
• iNO is safe and efficacious therapy for term and
near term infants with PPHN
• iNO may reduce the risk of BPD and brain injury
in some preterm infants
• iNO may increase the risk of death or IVH in some
preterm infants
• Further clinical trials are needed to determine
which preterm infants are most likely to benefit (or
be harmed) from iNO therapy
• In preterm infants (<35 weeks) treatment with iNO
to prevent BPD should only be used as part of a
randomized controlled clinical trial with informed
parental consent

46. Extracorporeal membrane
oxygenation (ECMO)
• Form of cardiorespiratory support that
allows the lungs to rest so also called
extracorporeal life support (ECLS)
• ECMO is given as a last resort when
everything else has failed
• Requirements
– > 33 weeks gestational age
– potentially reversible lung disease
– no bleeding disorders
– no intraventricular hemorrhages

47. Extracorporeal membrane
oxygenation (ECMO)
• OI>40 or PaCO2>12kPa for more than 3h
• ECMO 68% survival
• Conventional 41% survival
• UK Collaborative randomized trial of
neonatal ECMO 1996
• Recent decrease in ECMO due to more
widespread use of HFOV and iNO

48. PPHN Outcome
• PPHN may last a few days to several
weeks
• Mortality rate is 20-50%
– Decreased by HFOV and NO
– Decreased by ECMO
• Babies treated with hyperventilation have
high risk to develop sensorineural hearing
loss

49. Thank you…..