Hamid Rezvanian.MD
Neonatologist
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Failure of normal cardiopulmonary transition
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marked pulmonary hypertension
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right-to-left shunting of blood through fetal
circulatory pathways and hypoxemia
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The most critical signals for transition are:
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Mechanical distension of the lung
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Rising pO2 in the lungs
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Lowering pCO2
PPHN
6
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birth asphyxia
MAS
early-onset sepsis
RDS
hypoglycemia
Polycythemia
maternal use of nonsteroidal anti-inflammatory drugs
with in utero constriction of the ductus arteriosus
maternal late trimester use of selective serotonin
reuptake inhibitors
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pulmonary hypoplasia due to diaphragmatic hernia,
amniotic fluid leak, oligohydramnios, or pleural effusions
Idiopathic
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low plasma arginine and NO metabolite concentrations
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polymorphisms of the carbamoyl phosphate synthase gene
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higher plasma concentrations of the vasoconstrictor
endothelin-1
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PPHN should be suspected in all post term,term
and late preterm infants who have cyanosis and
respiratory distress
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Hypoxemia& cyanosis is universal
unresponsive to 100% oxygen
responsive transiently to hyperoxic hyperventilation
A Pao2gradient of preductal (right radial artery) and
apostductal (umbilical artery) sampling >20 mm Hg:
right-to-Ieft shunting through the ductus arteriosus
oxygenation saturation gradient >5% between
preductal and postductal sites on pulse oximetry
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holosystolic murmur of tricuspid or mitral
insufficiency
accentuated and not splitted 2nd heart sound
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Blood gas
CBC
B/C
BS,Ca
Serum electrolytes
Coagulation tests
oxygenation index (OI)
alveolar-arterial Po2 gradient (PAo2 - Pao2)
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normal findings In chest roentgenogram of asphyxiaassociated and idiopathic PPHN, (black lung PPHN)
parenchymal opacification and bowel and/or liver in the
chest in pneumonia and diaphragmatic hernia,
respectively
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echocardiogram plays an essential diagnostic role
and is an essential tool for managing newborns with
PPHN
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magnetic resonance imaging (MRI)
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Chest computed tomography (CT)
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Angiography
1.
oxygen administration( as a potent vasodilator), The
targeted PaO2 goal is between 50 and 90 mmHg (oxygen
saturation >90 percent)
2.Correction of hypoglycemia, acidosis, hypotension,
hypercapnia
3. maintaining a normal body temperature
4. Exogenous surfactant therapy( if needed ,improve lung
function)
5.maintenance of a hemoglobin concentration between 15
and 16 g/dL
6.minimal stimulation and the use of invasive procedures
7.Close monitoring of oxygenation ,BP, perfusion
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avoid rapid infusion of colloid or crystalloid solutions (
unless there is evidence of intravascular depletion)
dopamine is frequently first-line agent, in maintaining
adequate cardiac output and systemic blood pressure
dobutamine and milrinone, are helpful when myocardial
contractility is poor.
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overwhelming illness and relative adrenal insufficiency
cause hypotension refractory to vasopressor
administration:
Hydrocortisone is useful in such cases
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1.
2.
3.
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The goal of mechanical ventilation :
maintain normal functional residual capacity (FRC)
recruiting areas of atelectasis
avoid overexpansion.
overexpansion can elevate PVR, aggravate right-toleft shunting, and increase the risk for
pneumothorax
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Currently, no hyperventilation and/or
alkalinization
"gentle ventilation" with normocarbia or
permissive hypercarbia results in excellent outcomes
and a low incidence of chronic lung disease.
In this strategy maintain:
- Pao 2 between 50 and 70 mm Hg
- Paco2 is allowed to increase as high as 60 mm Hg.
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reducing barotraumas and associated air leak syndrome.
consider HFV In newborns with severe parenchymal lung
disease who require high peak inspiratory pressures (ie,
>30 cm water) or mean airway pressures (>15 cm water)
the goal should be to optimize lung expansion and FRC
and to avoid overdistention
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Agitation may cause catecholamine release, resulting in
increased PVR
opioid analgesics ( morphine sulfate & fentanyl) may
decrease sympathetic tone during stressful interventions
and maintain a more relaxed pulmonary vascular bed
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Routine adminstration of muscle relaxants not advised
1.atelectasis of dependent lung regions(reduce functional
residual capacity and pulmonary compliance)
2. ventilation- perfusion mismatch
3. increased risk of death
4. In congenital diaphragmatic hernia (CDH), prolonged
administration of pancuronium is associated with
sensorineural hearing loss and acute myopathy.
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NO is a rapid and potent selective pulmonary
vasodilator that can be delivered through a ventilator
Treatment with iNO is indicated for newborns with
an oxygen index (OI) of 25 or more despite maximal
respiratory support
OI = [mean airway pressure x FiO2 ÷ PaO2] x 100
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The optimal starting dose ,20 ppm ,reduces the need for
ECMO support by approximately 40%.
iNO did not reduce mortality, the length of
hospitalization, or the risk of neurodevelopmental
impairment.
Potential toxicity of iNO includes methemoglobinemia ,
pulmonary injury , and contamination of ambient air,
prolonged Bleeding times
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Contraindications include:
-congenital heart disease characterized by left ventricular
outflow tract obstruction (eg, interrupted aortic arch,
critical aortic stenosis, hypoplastic left heart syndrome)
-severe left ventricular dysfunction
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In 5-10% of patients with PPHN,the response to
100% oxygen, mechanical ventilation, and drugs is
poor and require ECMO
vasodilators: such as tolazoline, nitroprusside,
prostaglandin E 1(PGE 1 ), and prostaglandin D
(PGD)
 Although all these medications are efficacious in
lowering pulmonary vascular resistance, their use is
severely limited by
1.a lack of pulmonary selectivity
2.Systemic vasodilation , Leading to hypotension,
compromised tissue perfusion, and inadequate
oxygen delivery to vital organs.
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Therapy with continuous inhaled or intravenous
prostacyclin (prostaglandin I) has improved oxygenation
and outcome in infants with PPHN
The experience in neonates is limited but encouraging, and
it can emerge as a treatment in selected neonates with
chronic pulmonary hypertension
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Calcium channel blockers are of no benefit
Magnesium sulfate promotes vasodilatation by
antagonizing the entry of calcium ions into the
smooth muscle cells
Magnesium sulfate does not have a selective
pulmonary vasodilator effect.
The use of magnesium sulfate cannot be encouraged.
1.Sildenafil,PDE5 inhibitor selectively reduce pulmonary
vascular resistance
-Oral, aerosolized and parentral sildenafil were been
successful in the treatment of infants with PPHN
-The most common adverse event was hypotension
-Additional studies are needed to assess the safety and
efficacy of sildenafil
2.Milrinone a phosphodiesterase 3 inhibitor in infants
refractory to iNO has improved
-Responsiveness
-vascular dilation
-oxygenation
-attenuate rebound effect in some infants upon withdrawal of
iNO
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Bosentan an endothelin-1 receptor antagonist, was
reported to be effective and safe in
-improving OI and oxygen saturation
-decreasing the time of mechanical ventilation
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Fasudil :
-inhibitor of Rho kinase (production of O2reactive
species, vasoconstriction and remodeling of
pulmonary vessels)
-Effective in animal study
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Enhancers of NOS Activity
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Direct soluble guanylate cyclase activators
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Prostacyclin analogues
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Antioxidants
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Slow and gradual weaning of ventilator and vasodilator support results
in preventing of shunt recurrence
Neurologic evaluation by a neurologist & brain computed tomography
(CT) scanning or magnetic resonance imaging (MRI)
comprehensive cardiologic evaluation and an individual treatment plan
for patients with persistence of any level of pulmonary hypertension.
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hearing test before discharging the patient
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Feeding support :TPN &Nasogastric (NG) feeding
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Speech therapy may be helpful in reestablishing normal patterns of
feeding
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Reassessment of hearing at aged 6 months and again as
the results indicate
Close developmental follow-up for the first 2 years of life
complete screening before school enterance to determine
any subtle deficits that may predispose them to learning
disabilities
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