Persistent Pulmonary Hypertension of the Newborn PPHN

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Persistent Pulmonary Hypertension of the Newborn
(PPHN)

• Alona Bin-Nun, MD
• University of Chicago

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• Fetal circulation
• Characteristics
• Classification
• Physiology
• Diagnosis
• Treatment
• Prognosis

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• Adult circulation operates in series.
• All venous return passes through the right side ?
  lung (gas exchange) ? Oxygenated blood ? left
  side ? systemic circulation for oxygen delivery
  to the tissues.
• No mixing occurs between the two sides.

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• The fetal circulation operates in parallel.
• Both the right and left ventricles eject blood
  into the aorta with subsequent perfusion of the
  placenta.
• The right ventricle is dominant, and blood is
  shunted right-to-left through the foramen ovale
  and ductus arteriosus, mostly bypassing the lung,
  (not participating in gas exchange).

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• blood pressure in the lungs ? ? blood in the
  pulmonary artery is sent away from the lungs to
  the other organs through the ductus arteriosus.

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• A dramatic decrease in pulmonary vascular
  resistance is central to the process of
  transition to the extrauterine circulation.
• The decline in the PVR/SVR ratio results in a
  steady increase in pulmonary blood flow and
  oxygen uptake in the lung.
• The mediators stretching of the lung, O2 ,
  vascular endothelial factors.

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• PPHN also known as
• Persistent Fetal Circulation (PFC)

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PPHN - characteristics

• Failure to initiate or to sustain the transition
  from fetal circulation to neonatal circulation.
• Occurs primarily in term or near-term infants gt
  34 weeks gestation.
• ? pulmonary vascular resistance and a variable
  degree of right-to-left shunting across the fetal
  channels (PFO, PDA).

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PPHN cont.

• Hypoxemia, respiratory distress
• Diversity of underlying causes.
• Incidence 21000
• Mortality 11 (4-33)

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PPHN Potential Mechanism

• ? release of endogenous vasodilators NO, PGI2,
  Adenosine
• ? production of vasconstrictors (endothelin-1,
  thromboxane, PAF)
• Altered Vascular smooth muscle cells
  responsiveness

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PPHNClassification

• Maladaptation
• 2. Excessive muscularization
• 3. Underdevelopment
• 4. Flow obstruction

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1. Maladaptation

• Pulmonary vessels have undergone normal
  structural development.
• Failure of transition from fetal to neonatal
  circulation.
• Acute ? of pulmonary vascular resistance.
• Acute vascular vasoconstriction under conditions
  of acute stress meconium aspiration syndrome
  (MAS) 41, perinatal asphyxia iatrogenic stress.

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Maladaptation- cont.

• Hypoxia and/or acidemia 2o to airway obstruction,
  atelectasis ,RDS 13, alveolar hypoventilation.
• Release of vasoactive substances as in sepsis or
  tissue injury (pneumonia -14).

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2. Excessive muscularization

• Prenatal disturbances ?
• ? medial wall thickness of muscular intra acinar
  arteries and extension of muscularization of the
  medial smooth muscle layer into usually non
  muscular peripheral pulmonary arterioles ?
• interfere with postnatal pulmonary vasodilataion.

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Excessive muscularization cont.

• Chronic intrauterine stress and hypoxia
• Prenatal pulmonary hypertension
• Antenatal NSAIDs ? constriction of DA
• Antenatal SSRIs
• Fetal systemic hypertension
• Idiopathic

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• In the pulmonary hypertensive lung there is
  progression of muscularization into the
  non-muscular terminal portion of the arterial
  tree. This is due to hyperplasia and
  redistribution of smooth muscle cell.

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3. Underdevelopment

• ? in the total number of pulmonary vessels.
• 1. Space occupying lesions in the chest (CDH
  -10, cysts, pleural effusion, cong. cystic
  adenomatoid malformation)
• 2. Hypoplasia of lungs as in Potters synd, or
  oligohydramnios (4)
• 3. Interference in vessel growth (drugs,
  idiopathic).

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• Potter synd. Chest with small lung volumes and
  constriction of the upper thorax, while flaring
  of the lower ribs is seen secondary to the
  distended abdomen.

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4. Flow obstruction

• ? blood viscosity polycythemia, IUGR
• TAPVR and other rare congenital heart defects.
• Alveolar capillary dysplasia (misalignment of
  PVs)

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Physiology

• PFO and PDA protect the neonate with PPHN.
• In the case of absent shunts PVR gt SVR, RV
  might not be able to generate the pressure
  required to overcome the high resistance ? ? RV
  output ? ? pulm. blood flow ? ? LV filling ? ? RA
  pressure and ?sys. BP

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• R?L shunting through PFO ?
• LA filling ?
• ? Lt Cardiac output ?
• ? systemic BP and adequate perfusion with
  hypoxemic blood ? tissue extraction of O2

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Diagnosis

• Presence of risk factors (not in Congenital Heart
  Disease - CHD)
• 2. Physical examination limited (similar to
  babies with CHD like transposition of the great
  arteries).
• Sometimes prominent precordium, resp. distress,
  mec. staining.

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• 3. CXR helpful in identifying associated
  pulmonary disorders
• parenchymal disease (MAS).
• Air leak.
• Congenital diaphragmatic hernia.

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Diagnosis cont.

• 4. Preductal (rt. arm) and postductal blood gas
  measurement or O2 saturation
• If PDA shunting only
• preductal almost normal PaO2 and O2 sats post
  ductal lower PaO2 and O2 sats.
• A gradient in oxygenation confirms the diagnosis
  of PPHN.
• If PFOPDA shunting
• preductal post ductal lower PaO2 and O2 sats.

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Diagnosis cont.

• 5. Echocardiography definitive structural
  diagnosis.
• Doppler R?L shunting through the PDA or PFO.
  Tricuspid jet (insufficiency).

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Treatment

• Identify risk factors and anticipate potential
  illness (e.g. infants depressed at birth
  monitored to ensure adequate oxygenation)
• Supportive
• Goal
• Lower pulmonary vascular resistance.
• Maintain adequate tissue oxygenation.

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Treatment pulmonary

• Proven therapies
• Oxygen 100! May reverse pulmonary
  vasoconstriction.
• PaO2 50-90 mmHg (O2 sat gt90) to provide
  adequate tissue oxygenation and avoid lung
  injury.

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• Surfactant for RDS and MAS.

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• Potentially beneficial therapies
• Assisted ventilation
• Hypercarbia acidosis ? PVR maintain normal
  ventilation (PaCO2 35-40). When the infant
  stabilizes maintain PaCO2 40-50 (? lung injury
  associated with high volumes).
• In the past, hyperventilation was used. This
  intervention has not been tested.

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• Lung disease atelectasis and the resulting
  maldistribution of ventilation ? PVR.
• Recruit atelectatic segments, maintain adequate
  lung volume, and ensure appropriate oxygenation
  and ventilation.
• No lung disease hypoxemia is caused by R?L
  shunting rather than ventilationperfusion
  imbalance. Hypoxemia may not respond to
  conventional ventilator maneuvers. ? MAP may
  impede cardiac output and ? PVR.
• ? MAP by using low inspiratory pressures and
  short inspiratory times.

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• When lung disease is severe HFOV (optimize lung
  volume and ? alveolar ventilation).

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Oxygenation Index

• OI mean airway pressure x FiO2 PaO2 x 100
• High OI severe hypoxemic respiratory failure.
• OI guides the timing of interventions such as iNO
  administration (gt25) or ECMO support (gt40).   
• When OI gt 25 transfer to center where HFOV,
  iNO, and ECMO are readily available

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• Unproven therapies
• Respiratory alkalosis (pH7.40-7.45) useful in
  inducing pulm. vasodilation

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Treatment Pharmacologic

• Proven therapies
• Inhaled Nitric Oxide. Induces endothelium derived
  relaxation, hence, a selective modulator of
  pulmonary vascular resistance.
• -Indication OIgt 25

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• iNO ? pulmonary artery pressure and
  pulmonary-to-systemic arterial pressure ratio.
• Vasodilation in well-ventilated parts of the lung
  ? ? Oxygenation ? redistributing blood flow from
  regions with ? ventilation ? ? intrapulmonary
  shunting.
• iNO has little effect on SVR and systemic blood
  pressure.

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NO

• NO and its mechanism of action (? cyclic
  guanosine monophosphate) were discovered in the
  1980s.
• Selective pulmonary vasodilator when inhaled.
• Studies low dose (lt20 ppm) ? ?40 ECMO. HFOV
  iNO even more effective.
• Early studies in newborns with PPHN safety and
  efficacy.
• Larger studies iNO reduces ECMO and chronic lung
  disease in PPHN patients.

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• The initial dose of iNO 20 ppm.
• In infants who respond improvement of 20 in
  PaO2 or SaO2 within 15-20 minutes.
• The iNO is ? slowly as oxygenation improves.
• Patients require treatment for 3-4 days, some
  require more.
• Monitor for potential toxic effects by measuring
  the serum methemoglobin concentration, levels of
  NO2.
• Rapid withdrawal of iNO can cause profound
  hypoxemia.

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• Alternative treatments, like Sildenafil, have a
  role in the treatment of PPHN and MAS. These
  drugs could also have an additive effect to iNO
  by different mechanism of action.

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Treatment Pharmacologic- cont

• Unproven therapies
• Alkali infusion
• Tolazoline
• Intravenous vasodilators (prostacyclin)

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Treatment Cardiac support

• Proven therapies
• Support of cardiac output (dopamine, fluid) in
  severely affected patients
• ? PVR ? SVR or ? cardiac output ? ?
  systemic BP ? ? R ? L shunting.

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Treatment - Enviromental

• Potentially beneficial therapies
• Avoidance of noise
• Reduce light
• Unproven therapies
• Sedation (morphine, fentanyl) Infants may
  breathe out of synchrony with the ventilator and
  be agitated? catecholamine release ? ? PVR.

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• Paralysis (pancuronium) If dyssynchronous
  breathing persists.
• Limit this intervention as much as possible
  because of potential adverse effects. (? risk of
  death?).
• Prolonged skeletal muscle paralysis ? functional
  residual capacity and pulmonary compliance.

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Treatment Rescue

• Proven therapies
• ECMO

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• 40 of infants with severe PPHN require ECMO.
• The goal adequate tissue oxygen delivery and
  avoid irreversible lung injury while PVR ? and
  pulmonary hypertension resolves.
• Criteria when OI is consistently 40.
• Most patients with PPHN on ECMO 5-7 days.
• Patients who fail to improve may have an
  irreversible condition, such as alveolar
  capillary dysplasia or severe pulmonary
  hypoplasia.

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Prognosis
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• Survivors of severe PPHN and/or ECMO treatment
  are at increased risk of developmental delay,
  motor disability, and hearing deficits.
• 1/3 of the infants have at least one
  disability.
• All infants with severe PPHN who have been
  treated with iNO and/or ECMO should have
  neurodevelopmental follow-up.

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