1. Pulmonary hypertension in
neonates
Dr Varsha Atul Shah

2. What is the problem?
• PPHN / PFC : Persistence of the pattern of fetal
circulation postnatally due to a sustained elevation of
pulmonary vascular resistance, with right-to-left shunt
at the ductus arteriosus or foramen ovale in the
absence of structural heart disease
• Incidence: About 1 per 1000. Exact incidence unknown
in the absence of ICD coding or a “gold standard” for
diagnosis
• Mortality and Morbidity: Mortality rate of > 50% in the
absence of ECMO, and >10-20% with ECMO; >20%
severe handicap/intracranial hemorrhage/deafness
(Walsh-Sukys M C: Persistent pulmonary hypertension of the newborn. The black box revisited.
Clin Perinatol 20: 127-143, 1993)

3. Causes of PPHN
(Geggel RL, Reid LM:
The structural basis of PPHN.
Clin Perinatol 11:525-549, 1984)
PPHN
Normal Arterial Number Decreased Arteries e.g. CDH
Normal muscularization Increased muscularization
Maladaptation due
to acute injury
Developmental Chronic injury Malform-
(commonest) e.g.
immaturity with vascular ation
Sepsis, Meconium
aspiration synd., remodeling
asphyxia

4. Clinical features of PPHN
• Usually a term infant, with risk factors of
asphyxia, elective C/section without labor,
meconium stained fluid, sepsis, diaphragmatic
hernia etc. Some infants have no obvious risk
factors (idiopathic PPHN).
• Cyanosis due to shunting of blood from right to
left (pulmonary to systemic circulation)
“persistence of fetal circulation”, causing mixing
of deoxygenated with oxygenated blood

5. Clinical features of PPHN
• Right to left shunting of blood occurs most often
through the ductus arteriosus, and hence
saturation will be lower (by 10-15% or more) in
legs (+ left upper limb) as compared to right
upper limb and head
• In some infants, shunting of blood also occurs
within the heart at the foramen ovale level, and
hence SpO2 is the same in all limbs
• Confirmation of the diagnosis is by
echocardiogram, which will demonstrate R to L
shunting, elevated R sided pressures, and
absence of structural heart disease

6. Current management
Confirm diagnosis of PPHN
Correct underlying abnormalities (hypothermia, acidosis,
hypocalcemia, hypoglycemia, polycythemia); Oxygen by hood
Conservative mechanical ventilation
Trial of hyperventilation
If low PO2, trial of rescue therapies
Metabolic HFV Surfactant Vasodilators ECMO
Alkalosis NO, PGD2,
PGI2, Tolazoline,
Adenosine

7. Pathophysiological basis
of current management
• Mechanical ventilation:
 Ventilation-Perfusion (V/Q) matching to improve
oxygenation
 respiratory alkalosis to reduce Pulmonary Vascular
Resistance (PVR)
• Metabolic alkalosis: effect of pH on PVR
• Vasodilators: specific relaxation of the
pulmonary vasculature. Most experience with
Nitric Oxide
• ECMO: modified long-term cardio-pulmonary
bypass

8. Other support measures
• Cardiac strategies:
 Support of cardiac output and SVR with
dopamine, fluid infusions
• Environmental strategies:
 Sedation with fentanyl or morhphine
 Avoidance of noise and light stress

9. Ventilatory management
• ventilator management controversial
• FiO2 adjusted to maintain PaO2 80-100
to minimize hypoxia-mediated
pulmonary vasoconstriction
• ventilatory rates and pressures adjusted
to maintain mild alkalosis (pH 7.5-7.6),
usually combined with bicarbonate
infusion
• avoid low PaCO2 (<20 mm Hg) to
prevent cerebral vasoconstriction

10. Nursing care of infant with
PPHN
• Sedation (+ muscle relaxant) initially, wean as
condition improves. Too rapid or too slow
weaning are both bad.
• Minimal stimulation
• Close monitoring, esp. SpO2, PaO2, PaCO2. Hourly,
shift, or daily ranges and plan essential.
• Do not suction unless necessary! (e.g. MAS, thick
secretions). Suctioning can cause pain, fighting
ventilator, atelectasis, loss of lung volume
• Cannot hear heart sounds/breath sounds/bowel
sounds when on HFV. Use monitors!

11. Ventilator settings: PIP
• affects MAP (PO2) and VT (PCO2)
• PIP required depends largely on
compliance of respiratory system
• Clinical: gentle rise of chest with
breath, similar to spontaneous breath
• Minimum effective PIP to be used. No
relation to weight or airway resistance
• Neonate with PPHN: 15-30 cm H2O.
Start low and increase.

12. Ventilator settings: PEEP
• affects MAP (PO2), affects VT (PCO2) depending
on position on P-V curve
Volume
PEEP PIP
Pressure
• older infants (e.g. BPD) tolerate higher levels
of PEEP (6-8 cm H2O) better
• RDS: minimum 2-3, maximum 6 cm H2O.

13. Ventilator settings: Rate
• affects minute ventilation (PCO2)
• In general, rate ---> PCO2
• Rate changes alone do not alter MAP
(with constant I:E ratio) or change PO2 ,
unless PVR changes with changes in pH
• However, if rate --> TE < 3TC
--> gas trapping--> decreased VT--
> PCO2
• Minute ventilation plateaus, then falls

14. Ventilator settings: TI and TE
• Need to be 3-5 TC for complete inspiration
and expiration (Note: TC exp = TC insp)
• Usual ranges: TI sec TE sec
 RDS 0.2-0.45 0.4-0.6
 BPD 0.4-0.8 0.5-1.5
 PPHN 0.3-0.8 0.5-1.0
• Chest wall motion / VT may be useful in
determining optimal TI and TE

15. Ventilator settings: I:E ratio
• When corrected for the same MAP, changes in
I:E ratio do not affect gas exchange as much as
changes in PIP or PEEP
• Changes in TI or TE do not change VT or PCO2
unless they are too short (< 3 TC)
• Reversed I:E ratio: No change in mortality or
morbidity noted in studies. Not often used. May
improve V/Q matching and PO2 at risk of
venous return and gas trapping

16. Ventilator settings: FiO2
• affects oxygenation directly
• with FiO2 <0.6-0.7, risk of oxygen
toxicity less than risk of barotrauma
• to improve oxygenation, increase FiO2
to 0.7 before increasing MAP
• during weaning, once PIP is low
enough, reduce FiO2 from 0.7 to 0.4.
Maintenance of adequate MAP and V/Q
matching may permit a reduction in
FiO2

17. Ventilator settings: Flow
• affects pressure waveform
• minimal effect on gas exchange as long
as sufficient flow used
• increased flow--> turbulence
• higher flow required if TI short, to
maintain TV
• flow of 8-10 lpm usually sufficient
• change of flow may affect delivery of
NO or anesthesia gases

18. High frequency ventilation
HFPPV HFJV HFFI HFOV
VT >dead sp > or < ds > or <ds <ds?
Exp passive passive passive active
Wave- variable triangular triangular sine wave
Form
Entrai- none possible none none
ment
Freq. 60-150 60-600 300-900 300-3000
(/min)

19. High Frequency Ventilation in
PPHN
• V/Q matching to improve oxygenation
• Respiratory alkalosis to reduce PVR
• Improved response to inhaled NO
• “Rescue” for air leak syndromes

20. High frequency ventilation
• HFPPV
 conventional ventilators with low-compliance
tubing
 ventilatory rates of 60-150/min
 not very effective: minute ventilation decreases
with high frequencies [If TI < 3 TC, VT
decreases.]
(Boros et al. Pediatrics 74: 487-492, 1984 )
 ventilator and circuit design are not optimal for
use at high frequencies

21. HFPPV

22. HFPPV

23. Jet ventilation (HFJV)

24. Oscillator (HFOV)

25. Flow interrupter (HFFI)

26. Which is best: HFOV, HFJV,
HFFI, HFPPV ?
• No good animal or human comparisons;
animal studies suggest HFV causes less
lung damage than CMV
• Many centers now use HFOV for term
infants with PPHN, rather than HFFI or
HFJV
• Not possible to state if one type of HFV is
better in human infants

27. ECMO

28. Hyperventilation in PPHN
No HV/Alk HV Alk HV+Alk p
Mortality% 4.4 6.8 9.5 9.8 0.67
ECMO% 33.3 13.6 44.6 34.2 0.01
Duration 7.8 7.2 7.8 12.6 0.001
ventilator (d)
Duration O2 (d) 11.1 11.5 11.9 17.5 0.001
O2 at 28 d 2.7 2.8 6.8 16.7 0.1
(Walsh-Sukys et al. Pediatrics 105:14-20, 2000)

29. HFV Indications
• Usually used as “rescue” therapy for infants not
improving/deteriorating on conventional
ventilator
• Response to HFJV or HFOV may depend on
disease pathophysiology:
 Pneumonia and RDS more likely to respond (70-90%)
 MAS (50%) and CDH (20%) less likely to respond
(Baumgart et al. Pediatrics 89:491, 1992; Paranka et al.
Pediatrics 95: 400, 1995; Stewart et al. Eur Respir J 9:1257,
1996)

30. HFV techniques: HFOV
• MAP: start 1-3 cm H2O higher than on IMV:
controls V/Q matching and oxygenation
• Frequency: 8-12 Hz
• Inspiratory time: 33%
• Amplitude: sufficient for visible chest motion:
main determinant of CO2 elimination
• Target ABG: pH 7.45-7.55, PaCO2 30-40, PaO2
80-100, HCO3 26-30

31. HFV techniques
• “High volume strategy” often used
 Useful in animal models and preterm infants with RDS
 Assessment of lung volume a problem (chest X-Rays not
accurate)
 Initial MAP 10-20% more than MAP on IMV.
 Increase MAP in 1-3 cm H2O increments until oxygenation
and a/A ratio improve or cardiac compromise occurs
 FiO2 can then be weaned to 0.3-0.4. As lungs improve,
wean MAP slowly (MAP changes may take > 1 hr to affect
PaO2). If air leak, wean FiO2 later.

32. HFV + NO; HFV+
Surfactant
• The combination of HFOV and NO is more
effective than HFOV alone or NO alone
• HFV and surfactant prevent lung injury
synergistically, combination:
 prolongs efficacy of surfactant
 reduces number of surfactant doses
 reduces pulmonary morbidity

33. Summary
• PPHN is a rare but serious illness in
newborn infants
• Close monitoring and a staged approach
(oxygen by hood  IMV  HFV / NO 
ECMO) improve outcomes
• Most infants (>85%) now have normal
outcomes, except for infants with
diaphragmatic hernias.