Persistent pulmonary hypertension of the newborn (PPHN) complicates 10% of neonatal respiratory failures and can lead to mortality in 5-10% of cases. It is characterized by profound hypoxemia due to abnormally constricted pulmonary vasculature. Clinical evaluation involves assessing for pulmonary and cardiac causes through history, exams, oxygen responsiveness testing, and echocardiogram. Management follows a physiological approach including lung recruitment, selective pulmonary vasodilation, and optimizing cardiac function and hemodynamics often guided by echo and using vasodilators like iNO, prostaglandins, and milrinone along with inotropes. Refractory cases may require extracorporeal membrane oxygenation.

1. PPHN -diagnosis & management in the current era
Dr Amitava Sur

2. Case study
• Female, 35+4, singleton, PPROM since 20 weeks
• Profound hypoxemia , on HFOV @ 100%FiO2 , MAP 15
• Refractory hypotension on day 1
• Dopa +Dobu, Hydrocortisone. Multiple fluid boluses.
• MAP- 28-30mm,
• Bedside echo ..

4. Magnitude of the problem
• Neonatal respiratory failure affects 2% of all live births and
is responsible for 1/3rd of neonatal mortality
• PPHN (Persistent pulmonary hypertension) complicates
10% of all neonatal respiratory failures
• Severe PPHN - 2/1000 live births
• Even with appropriate therapy, the mortality for PPHN
remains between 5-10%.
• Approximately 25% of infants with moderate or severe
PPHN will exhibit significant neurodevelopmental
impairment at 12-24 months

5. Physiological mechanisms
mPAP = (PBF XPVR) + PCWP
L-R Shunts LV Dysfunction
Pulmonary vascular dysregulation
Abnormally constricted pulmonary vasculature due
to lung parenchymal diseases- MAS, RDS,
TTN,acute asphyxia
normal parenchyma and remodeled pulmonary
vasculature, also known as idiopathic PPHN. eg-
antenatal exposure to NSAID, SSRIs
Hypoplastic pulmonary vasculature- CDH,chronic
asphyxia

6. Clinical presentation- understanding hemodyanmics…
Low cardiac
output state
Hypotension
Metabolic
acidosis
Pre-post
ductal
difference
in PaO2,
SPO2
STATE OF IMPAIRED OXYGENATION AT PULMONARY AND
TISSUE LEVEL

7. Clinical evaluation & diagnosis
• Early onset hypoxemic respiratory failure with hypotension
secondary to underlying primary causes
• Careful assessment of history including maternal drugs, possibility of early
onset sepsis, meconium and perinatal asphyxia
• Pulmonary parenchymal cause vs vascular cause ? (difficult to rule out)
• 2 limb SPO2 (rt upper-lt lower ), hyperoxia, CXR- rule out CDH
• Are you missing a congenital duct dependent heart lesion ?
Duct dependent congenital cyanotic lesions like TAPC,
DORV & Hypoplastic Left Heart syndrome maybe be
worsened by strategies to reduce PVR and should be
excluded with confidence !!

8. Role of functional echo in PPHN
Assessment of PA
pressure & resistance
Assessment of RV
function
Assessment of LV
function
Quantitative:
Calculation of RV systolic
pressure from TR jet
RV contractility :
TAPSE
Tissue Doppler derived
myocardial velocity
LV preload:
Doppler flow across mitral
valve
Semiquantitative :
Serial monitoring of
PA systolic flow dopplers-
PA acceleration time/ejection
time
RV output calculation LV contractility :
EF, FS Simpson’s method
Qualitative :
Characteristics of motion &
shunt- septal motion, shunt
across PDA,PFO
LV output calculation
Jain, McNamara. 2015

9. Therapeutic approach…
• Treating the problem and not the consequence
• A-B-C approach
• Effective lung recruitment
• Selective pulmonary vasodilation
• Achieve normal CO and supra pulmonary systemic pressure (
essential to optimize contractility before aiming high MAP-
increased after load will be counterproductive )
• START REFERRAL PROCESS SIMULTANEOUSLY IF IN A
PERIPHERAL CENTRE

11. PATIENT
Minimal handling
Minimal noise
Optimal sedation

12. DON’T SHOOT IN THE DARK !!!

13. Physiological approach to PPHN
Identifying the underlying pathology
Primary parenchymal
disease, e.g.: MAS,
RDS,pneumonia
• Optimal ventilation &
lung recruitment, HFOV
• Avoid hyperoxemia
(paO2>80) & allow
permissive
hypercapnia
(paCO2=40-60mm)
• Surfactant
• Adequate sedation /
paralysis
• Monitor Oxygenation
Index (OI) >25- i NO,
>40- ECMO
Primary vascular
disease
• Selective pulmonary
vasodilators/ non
selective dilators
RV/LV dysfucntion
• Optimize
hemodynamics with
judicious use of
inotropes

14. Pulmonary vasodilators- cellular pathways and
options…
Its not a
piece of
cake !!!
SILDENAFIL
MILRINONE
ADENOSINE
Bosentan
i NO
Prostaglandins- Inhaled
(Iloprost), iv- Treprostanil
MgSO4

15. Optimizing RV function& hemodynamics…

16. nitric oxide..the magic molecule?
• Selective pulmonary vasodilator acting via CGMP pathway
• Selectively acts on aerated alveoli so optimal ventilation is a pre requisite
• Usual starting dose- 20ppm, weaning protocol.
• Short half life— forms MetHb with oxyHb. MetHb levels need monitoring on
long term use
• Few relative contraindications- rule out CCHD , qualitative platelet
dysfunction
• Relatively ineffective in chronic remodelled pulm vasculature unless
combined with other dilators as chronic use

17. Inotropes in PPHN- a random choice or evidence
based?
Dopamine vs Dobutamine ?
• Dopamine increases both SVR
and PVR in a dose dependent
manner
• A review by Barrington et al
concluded that Dopamine might
not be the ideal inotrope to start
in PPHN settings
• If using Dopamine DO NOT
exceed 10mic/kg/min
• Dobutamine is a better
cardiotrope as first line , might
require additional Epi/Norepi to
counter diastolic hypotension
• Problems??- Tachycardia—
impaired diastole— impaired
CO
Milrinone ?
• Mcnamara et al have shown in
their sentinel paper efficacy of
Milrinone in improving OI &
systemic BP
• Dose : Bolus @50mic/kg over
1 hr, titrate - (0.25-
0.9mic/kg/min)
• Problems: Systemic
hypotension, used in
combination with Epi/Norepi
• Milrinone+ Nor Epi - standard
accepted first line in PPHN in
UK
Mcnamara, Laique et al, Clin Res Ped
Vasopressin ?
• Low-dose AVP—
selective
vasodilatation in
pulmonary, renal,
coronary, and cerebral
vasculature under
hypoxic conditions
while causing
vasoconstriction in
other vascular beds
• V1 receptors induces
eNO
• Can be used in nitric
refractory PPHN
• Dose: 0.0002
u/kg/min

18. If reqmnt >10mic/kg/min , PPHN
confirmed- switch to Dobu/Milri+Nor Epi
If unsure of diagnosis, hypotensive-
start Dopamine
Add Milrinone (if not added in
previous step)
Vasopressin
Alternate vasodilators:
• NG sildenafil - 0.5-1mg/kg/dose Q6H
• MgSO4- 200mg/kg loading,50-100mg/kg/h
• Adenosine- 50mcg/kg/min
• Prostacyclin
Echo
Hydrocortisone

19. Key points when handling inotropes…
Rising lactate + cold extremities - consider easing off on adrenergic
drugs/ adding indicators like Milrinone
DO NOT aim for MAP> estimated PAP, aim for hemodynamic stability,
good perfusion and physiological lactates
Try to maintain HR <180, tachycardia impairs CO
Fluid balance should be titrated- overzealous bolus might damage
If available bedside Echo should be used to fine tune

20. PDA in severe PPHN-valve to the pressure cooker
• PDA acts as a “pop-off valve” to the ailing RV
• Sudden closure of the PDA in acute PPHN might decompensate
RV causing sudden increase in afterload
• Judicious use of Prostin at low doses is a standard in conditions
like CDH to keep the PDA open.

21. Key points in management of PPHN in resource limited
settings…
ABCDE
of
PPHN
Effective resuscitation
Alveolar recruitment
Managing hemodynamics (Echo guided)
• Obtain an arterial line
• Optimize ion balance- Ca, Mg
• Maintaining supra-pulmonary SBP
• Minimal boluses
• Inotropes- Choose wisely, Dobu+ NEpi
• Alternative& effective dilators-
• MgSO4 might be used early
Sedation- Fentanyl is
preferable
Paralysis- Continuous
infusion of Vecuronium
Quite surroundings
Minimal handling

22. If everything fails…
Extracorporeal Membrane Oxygenation (ECMO)

23. TR jet- explanation, measurement and fallacies
• Bernoulli’s principle: PG=4v2
• Pulm pressure=4v2 + RA pressure
• Found in 60-70% cases
• Dependent on respiratory cycle-
Right sided filling
• Dependent on RV-RA pressure
gradient, may be falsely decreased in
high RA pressures
• Affected by tachycardia, arrhythmia

26. • THANK
• YOU !!!!