Persistent Fetal Circulation: PPHN - Management, ECHMO.

1. By Dr Robin Thomas
Resident in Pediatrics
JJMMC, Davangere

2.  Defn :Disruption of normal perinatal to neonatal
circulatory transition-sustained elevation in
Pulmonary vascular resistance.
 Risk for chronic pulmonary disease &
neurodevelopmental disabilities.
 Incidence: 1-2 per 1000 live births.
 Perinatal risk factors: MSAF,
Maternal condn- fever, anemia, pulmonary d/s
Maternal D.M, U.T.I during pregnancy,
SSRIs, aspirin, NSAIDS & C.S

3.  Rapid fall in pulmonary vascular resistance
(PVR)-first breath & increase in systemic
vascular resistance (SVR) –clamping of
umbilical cord.
 Circulating biochemical mediators - increased
arterial O2 content & pH & lowered PaCO2 –
constriction of ductus- arteriosus &
vasorelaxation of pulmonary circulation.

4.  Physiological events raise SVR relative to PVR
–functional closure of foramen ovale.
 Persistent fetal circulation-mimics fetal
circulation-PVR exceeds SVR & right to left
hemodynamic shunting occurs tru foramen
ovale or ductus arteriosus.
 Dimnished pulmonary perfusion & systemic
hypoxemia.

6.  1.Severe fetal hypoxemia (Birth asphyxia) –
common association
 Prolonged fetal stress & hypoxemia –
remodeling & abnormal muscularization of
pulmonary arterioles.
 Acute birth asphyxia-release of
vasoconstricting humoral factors &
suppression of pulmonary vasodilators-
pulmonary vasospasm.

7.  2.Pulmonary parenchymal diseases-surfactant
deficiency, pneumonia, MAS.
 Fetus with advanced gestational age.
 3.Abnormalities of pulmonary dvp. – PPHN
Congenital diaphragmatic hernia, Porter
syndrome, Pulmonary parenchymal hypoplasia -
pruning of vascular tree.
Alveolar capillary dysplasia-malalignment of
pulmonary veins & arteries.

8.  4.Myocardial dysfunction, myocarditis,
intrauterine constriction of ductus arteriosus,
severe congenital heart disease-PPHN.
 5.Pneumonia or sepsis of bacterial or viral
orgin -PPHN. Suppression of endogenous NO
production.
endotoxin mediated myocardial depression,
pulmonary vasoconstriction assoc. with
release of thromboxanes.

9.  6.Familial recurrence-uncommon , infants
with PPHN –low plasma levels of arginine &
NO metabolites & specific polymorphism at
1,405 position of carbamoyl phosphate -
synthetase gene.

10.  1.Pulmonary vascular remodelling-abnormal
muscularization of non muscular intra-acinar
arteries with increased medial thickness of
larger muscular arteries-decreased cross
sectional area of pulmonary vascular bed &
elevated PVR.
 Fetal hypoxemia-stimulus for pulmonary
vascular remodelling.

12.  Humoral growth factors released by hypoxia
damaged endothelial cells promote
vasoconstriction & overgrowth of pulmonary
vascular muscular media.
 Vascular changes –fetal exposure to NSAIDS-
cause constriction of fetal ductus arteriosus &
fetal pulmonary overcirculation.

13.  2.Pulmonary hypoplasia
Affects both alveolar & pulmonary arteriolar
dvp.-congenital diaphragmatic hernia,
oligohydramnios syndrome, Porter syndrome
(renal agenesis).
 3.Reversible pulmonary vasospasm
Infants with nonfatal PPHN. Hypoxia induces
pulmonary vasoconstriction –acidemia.
Neural & humoral vasoactive substances.

14.  Suppression of endogenous NO, prostacyclin
or bradykinin production & release of
thromboxanes (A2,B2) , leukotrienes(C4,D4)-
increased PVR –Sepsis & hypoxemia.
 4. Myocardial dysfunction with elevated PVR-
1.Right ventricular dysfunction-
Intrauterine constriction of ductus arteriosus-
post natal pulmonary hypertension,
RV failure, atrial R-L shunt.

15.  2.Left ventricular dysfunction-pulmonary
venous hypertension & secondary pulmonary
arterial hypertension-right to left shunting
through ductus arteriosus.
 5.Mechanical factors
Cardiac output & blood viscosity.
Low cardiac output-fewer pulmonary
arteriolar channels & raises PVR.
Hyperviscosity with polycythemia-reduces
pulmonary microvasculature perfusion.

16.  Physical examn-cyanosis, prom. Precordial
impulse, single or narrowly split &
accentuated S2 , systolic murmur.
 Invest.
1.Gradient of 10 % or more in oxygen
saturation b/w preductal & postductal ABG or
transcutaneous O2 saturation- ductus
- arteriosus right to left hemodynamic shunt
& absence of structural heart disease-PPHN

17.  CXR-normal /assoc. pulmonary parenchymal
d/s.
 ECG-RV predominance-cons. normal for age.
 ECHO-hemodynamic shunting, evaluate
ventricular function, exclude congenital heart
disease.
TR or flattened ventricular septum in ECHO-
PPHN.

18.  Color doppler examn.-intracardiac or ductal
hemodynamic shunting.
 Continuous wave doppler sampling of
velocity of TR jet-estimate pulmonary artery
presures.

19.  Cyanotic congenital cardiac disease over
PPHN:
 cardiomegaly
 grade3 murmur
 weak pulses
 active precordium
 pulmonary edema
 pulse differ.b/w upper & lower extremities
 persistent preductal & postductal arterial O2
tension less or equal to 40 mmHg.

20.  Aim: reverse hypoxemia, improve pulmonary
& systemic perfusion, preserve end organ
function.
 Adequate respiratory support-normoxemia &
neutral to slightly alkalotic acid base balance
–facilitate normal perinatal circulatory
transition.

21.  1.Supplemental O2: Hypoxia-powerful
pulmonary vasoconstrictor
 Preductal & post ductal SaO2 should be
monitored.
Supplemental O2 –reduce abnormally elevated
PVR, minimize end organ underperfusion & lactic
acidemia.
 Maintain post ductal SaO2 >90%-ensure tissue
oxygenation & <98% to avoid hyperoxemia.

22.  2.Intubation & mechanical ventillation:
Hypoxemia persists despite maximal O2
admns. or respiratory failure-marked
hypercapnia & acidemia.
 Maintain PaO2 & PaCO2 values & avoid
hyperoxia & hyperventilation.
 Target goals: SaO2 90-98%, PaCO2 40-50
mmHg, pH 7.30-7.40

23.  a. PPHN with pulmonary parenchymal d/s-
HFOV high frequency oscillatory ventillation
or HFJV high frequency jet ventillation.
HFJV-useful for meconium aspiration
pneumonitis & air leak.
HFOV-deliver iNO.
 b.Absence of pulmonary disease-
High intrathoracic pressure impedes cardiac
output & elevates PVR.

26.  Strategy for mechanical ventillation-rapid,
low pressure, & short inspiratory time-
minimize elevated intrathoracic pressure.
 3.iNO –produced by endothelial cells.
diffuses into smooth muscle cells, increases
intracellular cGMP, relaxes vascular smooth
muscle & causes pulmonary vasodilation.

27.  iNO –HFOV-doses of 1-20 parts per million-
causes pulmonary vasodilation-not systemic-
vasodilation –decreases PVR.
 Methemoglobinemia-serious potential toxicity of
iNO Rx.
Measure metHb levels 24 hrs after start of Rx.
metHb levels>7% -reduce iNO
 Rebound hypoxemia-if iNO discontinued
abruptly.
 iNO should be tapered very gradually.

28.  Starting dose of iNO is 20ppm-delivered via
ventilator circuit.
 As baby improves & inspired O2 conc.<50%-iNO
is tapered by halving the dose.
eg: 20 to10 to 5 ppm over a 12-24 hr period -
gradually to 2 then 1 ppm.
 iNO –given in infants with PPHN & diffuse
pulmonary disease by concomitant use of HFOV
& surfactant treat.

29.  Sildenafil
 Phosphodiesterase-5 inhibitor
 Increases endogenous NO by inhibiting
metabolism-Rx for PPHN
 Randomized clinical trials awaited.

30.  4.ECMO
 Absence of pulmonary hypoplasia-ECMO-
life saving therapy for 75-85% infants with PPHN
who fail conventional management or iNO.
 ECMO criteria-
Alveolar arterial O2 difference (AaDO2)>600 or
Oxygenation index(OI)>30 on two ABGs >30 min
apart.
 Brief trial of HFOV or iNO instituted before ECMO.

31.  Technique of life support for neonates –cardiac
or respiratory failure-not responding to
conventional therapy.
 Indications: Respiratory failure-reversible,
Cardiac failure, E-CPR, Ex utero intra partum
treatment to ECHMO.
 Contra. Irreversible brain damage,
intraventricular & intraparenchymal hemorrhage,
wt<1.5kg, gestat. age<34wk, congenital abn.
severe coagulopathy, continuous CPR >1hr.

39.  5.Sedation & analgesia
 Fentanyl 1-4 micro gm/kg/hr infusion
 Morphine sulphate 0.05-0.1 mg/kg/hr
infusion-infant should not be hypotensive.
 6.Metabolic alkalosis
 Neutral to alkalotic pH-physiologic stimulus
that reduces PVR.
 Normalize pulmonary gas exchange &
conservative use of sodium bicarbonate.

40. 7.Hemodynamic support
a.Volume expansion
 0.9 % NS 10ml/kg over 20-30 min-used in
hemorrhage or excessive capillary leak,
Packed red blood cells also used.
 Infants with marked capillary leak-avoid 5%
albumin-albumin also leaks from capillaries –
worsen intertitial edema.

41. b.Pharmacologic Rx
 1.Cardiotonic agents-Dobutamine
 2.Vasopressors-Dopamine, Epinephrine.
 Milrinone-cardiac function very poor & infant
unresponsive to dobutamine.
enhances cardiac output & lowers PVR.

42.  Dobutamine-beta1 adrenergic stimulation.
 Dopamine-alpha & beta adrenergic receptor stimulation.
Support of systemic BP & improved cardiac output.
High dose 6-20 micro gm/kg/min
Moderate dose 3-5 micro gm/kg/min
Low 1-2 micro gm/kg/min- enhances mesenteric & renal
blood flow.
 Dopamine may increase PVR-high infusion rates >10micro
gm/kg/min.

43.  Epinephrine 0.03-0.10 micro gm/kg/min-
stimulates alpha & beta adrenergic receptors.
 Raises systemic BP tru enhanced cardiac
output & peripheral vasoconstriction.
 Epinephrine infusion caution-alpha
adrenergic receptor stimulation results in
pulmonary vasoconstriction & elevated PVR &
end organ (renal & mesenteric) perfusion
reduced.

44.  8.Correction of metabolic abnormalities
 Biochemical abnorm.-right to left shunting by
imparing cardiac function.
 Correction of hypoglycemia & hypocalcemia –
proper myocardial function.
 9.Correction of Polycythemia
 Hyperviscosity assoc. with polycythemia –
increases PVR –release of vasoactive
substances tru platelet activation.

45.  Partial exchange transfusion -central
hematocrit exceeds 65%.
 10.Additional pharmacological agents
 Sildenafil, adenosine, magnesium suphate,
calcium channel blockers, inhaled
prostacyclin, inhaled ethyl nitrite, inhaled or
inravenous tolazoline.
 Data insufficient to support use of these
medications.

46. 11.Treatment contraversies
 Interinstitutional variations in approach to
diagnosis & management of PPHN.
 Few centres report successful Rx without use
of mechanical ventillation, iNO, ECMO.

47.  PPHN results from disruption of normal
perinatal fetal to neonatal circulatory
transition.
 Incidence 1-2 per 1000 live births.
 Sustained elevation of PVR
 Persistent fetal circulation
 Contemporary ventilator management,iNO,
ECMO have improved survival among infants
with PPHN.

48.  Survivors of PPHN are at risk for chronic -
pulmonary disease , audiological,
neurodevelopmental or cognitive
impairments.

49.  1.Kliegman, Stanton, Geme ST, Schor, Behrman.
Nelson Textbook of Pediatrics 19th edition ,2012
:1529-1530.
 2.Cloherty PJ, Eichenwald CE, Hansen RA, Stark
RA. Manual of Neonatal Care 7th edition, 2012 :
435-442
 3.John FK, James EL, Donald CF. Nadas Text book
of Cardiology 2 nd edition 2006 :113-125
 4.Myung PK .Pediatric cardiology for Practitioners
2012, 5th edition:120-124