persistent pulmonary circulation in neonates

1. Dr. Chitti Babu Sontenam
MD,MRCPCH(UK)

2. LEARNING OBJECTIVES
 Understand key difference between fetal & neonatal circulations and
physiological transition at birth
 Definition -PPHN
 Etiology & Pathophysiology
 Diagnosis & Treatment
 take home message

3. FETAL CIRCULATION
 Lungs filled with fluid, no gas exchange
 the placenta is the organ of gas exchange
 pulmonary vasoconstriction > HIGH PVR due to low O2
 right-to-left >foramen ovale and ductus arteriosus,

5. TRANSITION AT BIRTH
PVR decreased
 lung fluid is replaced with air to establish gas exchange
 increase O2 which is potent vasodilator
 Rapid increase in pulmonary blood flow(8 to 10 fold)
SVR increased
 the umbilical cord is clamped> SVR
 closing FO & DA.

6. TRANSITION OF CIRCULATION AT BIRTH
 progressive fall in pulmonary vascular resistance (PVR)
 immediate rise in systemic vascular resistance (SVR)
FAILURE OF TRANSITION
 PVR > SVR
 SHUNTING RT > LT ( FORAMEN OVAL & DA)
 POOR XYGENATION

8. DEFINITION
 Persistent pulmonary hypertension of the newborn (PPHN) is defined as the
failure of the normal circulatory transition at birth.
 It is a syndrome characterized by marked pulmonary hypertension that causes
labile hypoxemia due to decreased pulmonary flow and right-to-left of blood.
 PPHN previously described as PERSISTENT FETAL CIRCULATION

10. EPIDEMIOLOGY
 The prevalence of PPHN -1.9 per 1000 live births
High risk factors for PPHN:
 GA 34 to <37 weeks (late preterm), Term, post-term
 Male infants
 LSCS
 Maternal diabetes

11. ETIOLOGY & PATHOGENESIS
PPHN
Three types of abnormalities of the pulmonary vasculature
 maladaptation ( secondary PPHN, most common type)
 underdevelopment
 maldevelopment

12. MALADAPTATION
PPHN secondary to lung parenchymal disease
 the pulmonary vascular bed is normally developed. However, adverse perinatal
conditions cause vasoconstriction and interfere with the normal postnatal fall in
PVR.
 MAS, RDS,TTN,Pneumonia,Sepsis,Perinatal asphyxia

14. UNDERDEVELOPMENT
pulmonary hypoplasia
 congenital diaphragmatic hernia (CDH),
 cystic adenomatoid malformation,
 Potter sequelae,obstructive uropathy,(severe oligihydromnias)
 uncommon but mortality risk is high.

15. MALDEVELOPMENT
 Idiopathic pulmonary hypertension accounts for approximately 10% of the
cases of PPHN.
 Normal lung parenchyma & no parenchymal lung disease.
 remodeling of their pulmonary vasculature, with vascular wall thickening
 hyperlucent lung fields on radiography(black lung PPHN).

18. CLINICAL MANIFESTATIONS
PPHN present within the first few hours of life(<8hrs)
 Hall mark- labile hypoxemia & RD
 Differential cyanosis
Pre – post ductal Spo2 difference >10% or Pao2 10-20mm Hg
Heart Signs-
Loud single 2ndsound & harsh systolic murmur(TR)

19. INITIAL LABORATORY TESTS
 Arterial blood gas
 Chest radiography.
 Gold standard- Echocardiography

20. ECHOCARDIOGRAPHY IN PPHN
 Direction of blood flow in DA & FO( Rt-to-Lt shunting)
 Flattened or Bowing of IVS
 Tricuspid regurgitation (TR) jet
 right ventricular dilatation,
 Exclude Cyanotic CHD

22. OXYGENATION INDEX(OI)
Severity of PPHN
 OI = [MAP x FiO2 ÷ PaO2] x 100
 OI < 15-20(mild)general supportive care
 OI ≥20-25(moderate)usually need HFOV & INO.
 OI >40 (severe)ECMO

23. DIFFERENTIAL DIAGNOSIS
Cyanotic congenital heart disease (CCHD)
Perinatal asphyxia
parenchymal lung diseases
Neonatal Sepsis

24. MANAGEMENT
 General supportive care.
 Specific treatment-vasodilators
 Extracorporeal membrane oxygenation (ECMO)

25. SUPPORTIVE MANAGEMENT
 Maintaining a normal body temperature
 Correction of acidosis
 Minimal stimulation/handling
 Sedation(fentanyl, morphine, midazolam)
 Paralysis should be avoided if possible due to increased mortality
 Maintain BP > GA

26. MECHANICAL VENTILATION
Almost always necessary for the newborn with PPHN.
The goal of mechanical ventilation
 Optimal lung recruitment
 Adequate lung expansion(8-9 ribs expansion on CXR)
Gentle ventilator strategies
 optimal PEEP, relatively low PIP/MAP or Tidal volume

27. HIGH FREQUENCY VENTILATION
Switching to high frequency ventilation
 If PIP > 25 to 28
 MAP >15
 Tidal volume >6ml/kg
 OI >20-25

28. TARGET OXYGEN & BLOOD GAS
 Maintaining preductal Spo2 90-97%
 Post ductal O2 saturation in 70s and 80s may be acceptable
 Ph >7.25,peferably 7.30-7.40
 Pao2:55-80)
 Pco2 40-50
 Serum lactate < 3 mM/Lt,
 UOP is adequate(>1ml/kg/hr)

29. SURFACTANT
 Recommended in infants with secondary PPHN
 Early administration associated with better outcome
 Reduces need for ECMO & Mortality
 Unclear whether surfactant is beneficial in CDH but recommended

31. SPECIFIC TREATMENT >PULMONARY VASODILATORS
 INO
 Sildanafil
 Milrinone
 Bosentan,Prostacyclins,Magnesium sulphate

32. INO
 Potent & selective pulmonary vasodilator
 Reduces PVR, increases perfusion & Optimizing V/P
 Marked improvement in oxygenation
 dose 20ppm(parts per million)higher dose not recommended
 improvement of 20% in pao2/spo2 occurs within 15-20min
 Safe, well tolerated, effective rescue therapy
 Reduces need for ECMO (30 - 40%)
 Duration typically <5days
 20-20-20 rule(OI-20,dose 20,improvement 20%)

35. WEANING
 FiO2 ≤ 0.6, PaO2 ≥ 60, SpO2 ≥ 92% for 60min, OI <10
Wean iNO down by 5ppm every 4hrs
reach 5ppm 1ppm Hourly if tolerated & switched off
Progressively wean FiO2
 60-60-60 rule

36. WEANING OF INO

37. INO PROBLEMS
 Approximately 30% non responders
 rebound effects
 dependence for weeks
 Methemoglobinemia shouldnot exceed >5%)
 Nitrogen dioxide

38. INO AND HFOV:
BETTER THAN EITHER ALONE IN PPHN

39. SILDENAFIL
If blood pressure is relatively stable but hypoxemia persists
 PDE 5 inhibitor > increase cGMP > vasodilatation
 Dose oral 1-2mg/kg/dose 6hrly(preferred),
 Reduced rebound pulmonary HT during INO weaning
 Hypotension,Careful monitoring of BP during therapy

41. MILRINONE
If BP is normal but evidence of ventricular dysfunction
 PDE3 Inhibitor >increase cAMP>relaxes pulmonary arteries
 Loading dose IV 50mcg/kg over 30-50min maintainance dose 0.3-1mcg/kg/min
 BP should be closely monitored due to systemic hypotension

42. OTHER VASODILATORS
 Bosentan
 Prostacyclins
 MgSo4
 Recombinant human superoxide dismutase(SOD)
 Apocynin - NADPH Oxidase inhibitor

43. OUTCOME & FOLLOW UP
 Mortality related to PPHN has been declining <20-25%
 Those who survive have long-term consequences like
 neurodevelopmental and cognitive impairment (25%)
 hearing difficulties(23%)
 Essential to provide long term multidisciplinary follow up

44. Premature infants
 Increasingly diagnosed in extremely PT infants
 Some with RDS presents with PPHN in first few days
 Some with BPD diagnosed PHN later distinct from PPHN with more protracted
course and it challenging with significant mortality
CDH
 Important cause of pulmonary hypoplasia resulting in PPHN
 Mortality and need for ECMO remain high
Alveolar capillary dysplasia.
 Malalignment of pulmonary vasculature
 Present with RF and unremitting PPHN carries 100% mortality
 Neonates who fail to respond consider lung biopsy to rule out

45. TAKE HOME MESSAGE
 PPHN is serious problem associated with with significant mortality & morbidity
 PPHN often secondary to parenchymal lung disease
 Diagnosis based on clinical and confirmed by ECHO
 Management has significantly improved in last 2decades
 Emphasis on gentle ventilator strategies for optimum lung recruitement
 INO and HFV improved outcome and reduce the need for ECMO

46.  THANKS FOR LISTENING