Persistent Pulmonary Hypertension (PPHN/PFC)of the Newborn

Dr.Sid Kaithakkoden MDMBBS,DCH,DNB,MD,MRCPCH,FCPS

alavisaid@aol.com

PPHN/PFC

• Disorder of the transitional circulation wherein unsaturated blood continues to bypass the lungs by way of the foramen ovale and/or the ductus arteriosus

• PPHN is the failure of PVR to fall at birth• The transition from fetal circulation to extra uterine

circulation is not complete

• R-L shunting occurs through a patent ductus arteriosus and foramen ovale

• Infants remain cyanotic after birth ( similar to those with cyanotic CHD)

Typically seen in:

• Full term or post term infants• 37-41 weeks gestational age• within the first 12-24 hours after birth

PPHN• Primary

– Normal cardiac anatomy, normal labs except for cyanosis

• Secondary – Meconium aspiration syndrome – Asphyxia – Sepsis (GBS, E. coli, etc) – Congenital diaphragmatic hernia – Congenital heart disease (rarely) – Others

Primary PPHN• Classical PPHN

– idiopathic

– Hypoxemia develops in a baby with normal lungs

– Breath sounds and CXR are usually normal

Possible causes• Chronic intrauterine hypoxia• Asphyxia• Maternal ingestion of prostaglandin

– Premature ductal closure– Mothers who took aspirin near term caused repeated

intrauterine closure of the ductus with redirection of blood into the pulmonary vasculature

• Hypoglycemia• Hypothermia• Maternal hypertension

Secondary PPHN• PPHN secondary to lung disease

– meconium aspiration syndrome– congenital diaphragmatic hernia– group B streptococcal pneumonia

– respiratory distress syndrome

– sepsis

– lung hypoplasia

Fetal Shunts• Ductus arteriosus

– R-L shunting of blood from pulmonary artery to the aorta bypasses the lungs

– Usually begins to close 24-36 hours after birth

• Foramen ovale– Opening between left and right atria– Closes when there is an increased volume of

blood in the left atrium

Ductus Arteriosus• Blood pumped from

the right ventricle enters the pulmonary trunk

• Most of this blood is shunted into the aortic arch through the ductus arteriosus

Foramen Ovale

• Blood is shunted from right atrium to left atrium, skipping the lungs

• More than one-third of blood takes this route

• Is a valve with two flaps that prevent back-flow

What happens at birth?• The change from fetal to postnatal circulation happens

very quickly• Changes are initiated by baby’s first breath

What Happens at Birth? (contd)

• With the first breaths of life, fetal lung fluid is cleared, FRC is established, surfactant is secreted

• Coincident with cord clamping, the low resistance placenta is removed and systemic resistance rises

• A rise in pO2 causes a fall in PVR, resulting in increased PBF

• Increased pulmonary venous return to the LA increases LA pressure, functionally closing the FO

• The increase in PBF, as well as the increase in pO2, decreases ductal level shunting

Foramen ovale Closes shortly after birth, fuses completely in first year

Ductus arteriosus Closes soon after birth, becomes ligamentum arteriousum in about 3 months

Ductus venosus Ligamentum venosum

Umbilical arteries Medial umbilical ligaments

Umbilical vein Ligamentum teres

Normal Pulmonary Vascular Transition

• The pulmonary vascular transition at birth is characterized by :– rapid increase in pulmonary blood flow

– reduction in PVR

– clearance of lung liquid

PPHN• Failure to achieve the normal decrease in PVR at

birth

• Altered pulmonary vascular tone, reactivity and/or structure

• Severe hypoxemia as a result of right-to-left shunting of blood across the DA and FO

• Common condition among infants requiring neonatal intensive care– 1-2 per 1000 live births– 10-20% mortality

Signs of PPHN• Infants with PPHN are born with Apgar

scores of 5 or less at 1 and 5 minutes

• Cyanosis may be present at birth or progressively worsen within the first 12-24 hours

Later developments• Within a few hours after birth

– tachypnoea– retractions– systolic murmur

– mixed acidosis, hypoxemia, hypercapnia

• CXR– mild to moderate cardiomegaly– decreased pulmonary vasculature

Pulmonary Vasculature• Pulmonary vascular bed of newborn is

extremely sensitive to changes in O2 and CO2

• Pulmonary arteries appear thick walled and fail to relax normally when exposed to vasodilators

• Capillaries begin to build protective muscle (remodeling)

Assessment of Infant with PPHN

• Airway Patency• Alveolar Recruitment• Underlying Pulmonary Vascular

pathology• Degree and level of shunt• Myocardial

– Filling volumes

– Contractility

– Structural abnormalities

PPHN• Diagnosis

– Hypoxemia poorly responsive to O2– ‘Differential cyanosis’

• Rt.radial - descending aorta diff. 1.33kPa or 5%

DiagnosisHyperoxia Test• Place infant on 100% oxyhood for 10

minutes.– PaO2 > 100 mmHg parenchymal lung

disease– PaO2= 50-100 mmHg parenchymal lung

disease or cardiovascular disease– PaO2 < 50 mmHg fixed R-L shunt cyanotic

congenital heart disease or PPHN

Hyperoxia Test (cont.)• If fixed R-L shunt

– need to get a preductal and postductal arterial blood gases with infant on 100% O2

• Preductal- R radial or temporal artery• Postductal- umbilical artery

– If > 15 mmHg difference in PaO2 then ductal shunting

– If < 15 mmHg difference in PaO2 then no ductal shunting

Echocardiography• PFO / PDA patent / RV strain / bulging

intraventricular septum• R → L (or bidirectional) shunt across PDA/• R ventricle may be larger than normal• increased pulmonary artery pressure• increased pulmonary vascular resistance

Treatment Goals:• Maintain adequate oxygenation

– These babies are extremely sensitive

– Handling them can cause a decrease in PaO2 and hypoxia

– Crying also causes a decrease in PaO2

– Try to coordinate care as much as possible

• Maintain neutral thermal environment to minimize oxygen consumption

Management (contd)

• Supportive• Avoid hypothermia, hypoglycaemia,

hypovolaemia, hypocalcaemia, anaemia• Correct metabolic acidosis• Treat underlying cause (e.g. sepsis)• ↑systemic arterial BP → ↓L to R shunt

Management (contd)

• Provide oxygen and ventilate • Sedate and paralyze • Vasodilator drugs • High frequency ventilation• Inhaled nitric oxide • ECMO

Vasodilator drugs• Tolazoline• Prostacyclin• Sodium nitroprusside• Verapamil• Nifedipine• Magnesium sulphate• Sildenafil• Adenosine

Tolazine– Pulmonary and systemic vasodilator

– pulmonary response needs to assessed by giving 1-2 mg/kg through peripheral vein

• if positive response- start continuous infusion of 0.5-1.0 mg/kg/hr

– Monitor closely for GI bleeding, pulmonary hemorrhage and systemic hypotension

– May need to also give Dopamine or Dobutamine to maintain systemic blood pressure and to increase CO

Management (contd)Respiratory• Avoid high PVR due to high or low lung volumes• Minimise risk of lung injury• Some may respond to:

– V.high lung volume strategy on HFOV– ‘open lung’ approach (high PEEP, low tidal volume)– Surfactant

• Avoid hyperventilation– Increases risk of VILI– Response to alkalosis likely to be transient– Increased risk of adverse neurodevelopmental outcome

due to ↓cerebral blood flow

HFOV• High frequency oscillatory ventilation

– decrease risk of barotrauma– effective alveolar ventilation– alveolar recruitment

• Nitric Oxide more effective

• HFOV more effective in PPHN babies with lung disease

5-20ppm improves oxygenation and reduces the need for ECMO in PPHN

Inhaled nitr ic oxide (iNO)

• cGMP is a second messenger of nitric oxide (NO)

• Stabilization of cGMP results in increasing nitric oxide (NO) at the tissue level leading to pulmonary vessel vasodilatation

• Nitric oxide has been considered the closest thing to an ideal vasodilator

Nitric oxide (NO) and prostacyclin (PG) signaling pathways in regulation of vascular tone

Recommendations for theuse of iNO

• Who to Rx: – Near term (>34 weeks) and term NB with OI>25, and

echocardiographic evidence of adequate CO and R L shunt

• Starting dose:– 20 ppm; Maximum dose: 20 ppm; Reduce to 5 ppm in first 4-24 h

• Duration: – < 5 days in most cases; exception – CDH

• Weaning: – Decrease to 5 ppm in first 4-24 h; Decrease by 1 ppm to 1 ppm

before discontinuing

• Discontinue: – When FiO2 < 0.6 and PaO2 >60 for 30-60 min on 1ppm; Increase

FiO2 by 10-15% before discontinuing iNO; Observe for rebound

Subtleties of iNO Use• Rebound can occur, even in non-responders

– This has implication for use of NO in non-ECMO centers and for transport

• Poor lung inflation with inadequate alveolar recruitment is the most common cause of treatment failure– HFOV combined with iNO resulted in less ECMO use

compared with either Rx alone

– Surfactant decreased the use of ECMO in RDS, MAS, and sepsis, but not idiopathic PPHN

iNO and PPHN: Summary• iNO reduces use of ECMO without influencing

LOS, ventilator days, long-term neurodevelopmental outcomes or mortality

• iNO is not efficacious in all infants with PPHN– 40% non-responders– Infants with CDH represent a therapeutic challenge

• Infants with parenchymal lung disease most likely to respond to combined therapy with iNO plus a lung volume recruitment strategy, such as HFOV, optimal PEEP, or surfactant therapy

iNO in the Premature Lung• iNO improves gas exchange, decreases PVR,

decreases lung neutrophil accumulation in the mechanically ventilated premature lamb with RDS (Kinsella et al, 1994, 1997)

• In the premature baboon, iNO improves early pulmonary function and favorably alters extracellular matrix deposition(McCurnin et al, 2005)

• iNO enhances distal lung growth in newborn animals exposed to hyperoxia (Lin et al, 2005) and mechanical ventilation (Bland et al, 2005)

Potential risks of iNO in thePremature Newborn• Prolongation of bleeding time (dose

dependent) with attendant risk of intracranial hemorrhage

• Decreasing pulmonary vascular resistance in presence of PDA could lead to pulmonary overflow, edema, hemorrhage

• Potential effects on surfactant function

Poor response to iNO

• Inadequate lung inflation• Severe pulmonary hypoplasia• Poor myocardial function / low

systemic BP• Wrong diagnosis

Summary and Conclusions• iNO is safe and efficacious therapy for term and

near term infants with PPHN• iNO may reduce the risk of BPD and brain injury

in some preterm infants• iNO may increase the risk of death or IVH in some

preterm infants• Further clinical trials are needed to determine

which preterm infants are most likely to benefit (or be harmed) from iNO therapy

• In preterm infants (<35 weeks) treatment with iNO to prevent BPD should only be used as part of a randomized controlled clinical trial with informed parental consent

Extracorporeal membraneoxygenation (ECMO)• Form of cardiorespiratory support that

allows the lungs to rest so also called extracorporeal life support (ECLS)

• ECMO is given as a last resort when everything else has failed

• Requirements– > 33 weeks gestational age– potentially reversible lung disease– no bleeding disorders– no intraventricular hemorrhages

Extracorporeal membraneoxygenation (ECMO)

• OI>40 or PaCO2>12kPa for more than 3h• ECMO 68% survival• Conventional 41% survival• UK Collaborative randomized trial of

neonatal ECMO 1996• Recent decrease in ECMO due to more

widespread use of HFOV and iNO

PPHN Outcome• PPHN may last a few days to several

weeks• Mortality rate is 20-50%

– Decreased by HFOV and NO

– Decreased by ECMO

• Babies treated with hyperventilation have high risk to develop sensorineural hearing loss

Thank you…..