Overview
Definition:
Persistent Pulmonary Hypertension of the Newborn (PPHN) is a clinical syndrome characterized by the failure of the normal circulatory transition from fetal to neonatal circulation, resulting in sustained elevated pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PPH)
This leads to shunting of blood through fetal pathways (foramen ovale, ductus arteriosus), causing systemic hypoxemia.
Epidemiology:
PPHN occurs in approximately 1-8 per 1000 live births
It is more common in term and post-term infants
Risk factors include maternal exposure to NSAIDs, SSRIs, gestational diabetes, fetal distress, meconium aspiration syndrome, and congenital diaphragmatic hernia.
Clinical Significance:
PPHN is a life-threatening condition requiring prompt diagnosis and management
Inadequate oxygenation and systemic perfusion can lead to multiorgan dysfunction, neurological damage, and increased mortality
Understanding iNO initiation and escalation is crucial for neonatologists and pediatric residents preparing for DNB and NEET SS exams.
Clinical Presentation
Symptoms:
Severe cyanosis unresponsive to increasing inspired oxygen
Tachypnea and grunting respirations
Tachycardia
Mottling and cool extremities indicating poor perfusion
Hypoxia with a significant gradient between pre-ductal (right arm) and post-ductal (legs) oxygen saturation (desaturations)
Murmur of a patent ductus arteriosus or tricuspid regurgitation may be present.
Signs:
Hypoxemia (PaO2 < 50-60 mmHg) that worsens with crying or exertion
Cyanosis
Tachypnea
Grunting
Retractions
Nasal flaring
Potential for right ventricular failure (e.g., hepatomegaly)
Peripheral pulses may be diminished
A bounding pulse in the lower extremities compared to the upper extremities may indicate a right-to-left shunt through the ductus arteriosus.
Diagnostic Criteria:
No single definitive diagnostic criterion exists, but diagnosis is typically made clinically supported by echocardiographic findings
Key elements include: 1
Severe hypoxemia disproportionate to the degree of lung disease
2
Exclusion of other causes of cyanosis (e.g., sepsis, congenital heart disease)
3
Echocardiographic evidence of elevated pulmonary artery pressure and right-to-left shunting across the ductus arteriosus or foramen ovale.
Diagnostic Approach
History Taking:
Maternal history: use of medications (NSAIDs, SSRIs), pregnancy complications (preeclampsia, diabetes, fetal distress), term of gestation
Neonatal history: onset of respiratory symptoms, response to initial oxygen therapy, presence of meconium staining, birth trauma.
Physical Examination:
A thorough cardiopulmonary examination focusing on: 1
Oxygenation: assessment of cyanosis, pre- and post-ductal saturation monitoring
2
Respiration: rate, effort, adventitious sounds
3
Hemodynamics: heart rate, blood pressure, peripheral perfusion, presence of murmurs
4
Abdomen: hepatomegaly suggesting RV dysfunction.
Investigations:
Arterial blood gases (ABGs): essential for assessing oxygenation and ventilation
look for hypoxemia and potential respiratory acidosis
Chest X-ray: often shows normal lung fields (idiopathic PPHN) or signs of underlying pathology (MAS, CDH)
Echocardiography: crucial for diagnosing PPHN, assessing pulmonary artery pressure, identifying shunting, and ruling out structural cardiac defects
CBC, blood cultures: to rule out sepsis
Metabolic screen: to assess for metabolic acidosis.
Differential Diagnosis:
Congenital heart disease (e.g., transposition of the great arteries, truncus arteriosus), sepsis with myocardial dysfunction, pulmonary hypoplasia, meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), pneumonia, birth asphyxia, pulmonary venous obstruction.
Management
Initial Management:
Immediate stabilization with adequate oxygenation and ventilation
Mechanical ventilation is often required, aiming for adequate oxygenation (PaO2 > 60 mmHg) and ventilation
Avoid hyperventilation if possible as it can cause cerebral vasoconstriction
Minimize painful stimuli and maintain normothermia
Fluid resuscitation and adequate nutrition are essential
Judicious use of inotropes (e.g., dopamine, dobutamine) if myocardial dysfunction is present.
Medical Management:
Inhaled Nitric Oxide (iNO): This is the cornerstone of medical therapy for PPHN
It is a selective pulmonary vasodilator
Initiation: Typically started at 20 ppm
Titration: If adequate response (improved oxygenation and reduced pulmonary pressure) is observed, iNO can be weaned
Escalation: If initial response is poor or absent, doses can be escalated cautiously up to 40 ppm
If no response at 40 ppm, other therapies should be considered
Weaning: Once stable, iNO is gradually reduced (e.g., 10 ppm for 1 hour, then 5 ppm for 1 hour) and then discontinued
Discontinuation should be slow to avoid rebound pulmonary hypertension.
Escalation Strategies:
If initial iNO at 20 ppm is ineffective, doses may be increased to 40 ppm
If there is still no adequate response, consider other vasorelaxant agents like sildenafil, bosentan, or even extracorporeal membrane oxygenation (ECMO)
Concurrent management of underlying causes (e.g., antibiotics for sepsis, surgery for CDH) is critical
High-frequency oscillatory ventilation (HFOV) may be beneficial in severe cases refractory to conventional ventilation and iNO.
Supportive Care:
Continuous pulse oximetry and blood pressure monitoring
Strict fluid management to avoid fluid overload
Nutritional support via parenteral or enteral routes as tolerated
Sedation and analgesia to minimize stress and oxygen consumption
Regular echocardiographic assessment to monitor response to therapy and reassess pulmonary pressures
Management of potential complications such as air leak syndrome or intraventricular hemorrhage.
Complications
Early Complications:
Rebound pulmonary hypertension upon iNO withdrawal
Bronchospasm
Methemoglobinemia (rare with current protocols)
Pulmonary edema
Air leak syndromes (pneumothorax)
Intraventricular hemorrhage
Necrotizing enterocolitis.
Late Complications:
Chronic lung disease (bronchopulmonary dysplasia)
Neurodevelopmental deficits (e.g., hearing loss, cognitive impairment, motor deficits) in survivors, particularly those with severe PPHN or requiring ECMO
Pulmonary hypertension persistence.
Prevention Strategies:
Aggressive management of underlying conditions
Careful titration and weaning of iNO
Close monitoring for methemoglobinemia and nitrogen dioxide
Judicious use of ventilation strategies to minimize barotrauma and volutrauma
Early identification and management of complications.
Prognosis
Factors Affecting Prognosis:
Severity of hypoxemia and systemic hypoperfusion
Presence and severity of underlying condition (e.g., CDH, MAS)
Response to iNO therapy
Need for ECMO
Duration of illness and ventilation.
Outcomes:
With optimal management, including iNO, survival rates for PPHN have improved significantly
However, long-term sequelae can still affect survivors, especially those with severe illness
Infants requiring ECMO have a higher risk of morbidity and mortality.
Follow Up:
All survivors of PPHN require close neurodevelopmental follow-up, including audiology assessments and developmental screenings
Pediatric cardiology follow-up may be necessary if residual pulmonary hypertension or cardiac anomalies are identified.
Key Points
Exam Focus:
iNO mechanism: selective pulmonary vasodilator
Initiation dose: 20 ppm
Maximum dose: 40 ppm
Common side effects: methemoglobinemia, nitrogen dioxide
ECMO as a rescue therapy for refractory PPHN
Differentiating PPHN from congenital heart disease on echo is critical.
Clinical Pearls:
Always check pre- and post-ductal saturation to assess shunt direction
Echocardiography is the gold standard for diagnosis and assessment of PPHN
Gradual weaning of iNO is crucial to prevent rebound
Consider sildenafil or bosentan if iNO is ineffective and ECMO is not indicated or available.
Common Mistakes:
Starting iNO without confirming PPHN with echocardiography
Aggressive hyperventilation leading to cerebral vasoconstriction
Abrupt withdrawal of iNO causing rebound
Inadequate management of underlying conditions contributing to PPHN.