Overview
Definition:
Persistent Pulmonary Hypertension of the Newborn (PPHN) is a clinical syndrome characterized by elevated pulmonary arterial pressure and vascular resistance, leading to shunting of blood through fetal circulatory pathways (foramen ovale, ductus arteriosus) and resulting in 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 meconium aspiration syndrome, pneumonia, asphyxia, congenital diaphragmatic hernia, and conditions associated with impaired pulmonary vasodilation.
Clinical Significance:
PPHN is a life-threatening condition requiring prompt diagnosis and aggressive management
Failure to adequately treat PPHN can lead to severe hypoxemia, end-organ damage (brain, kidneys, intestines), and increased mortality
Understanding the comparative efficacy and indications of therapeutic agents like sildenafil and inhaled nitric oxide (iNO) is crucial for pediatric residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Onset of respiratory distress typically within the first few hours to days of life
Cyanosis that worsens with crying and improves with oxygen administration
Tachypnea and grunting
Tachycardia
Hypotension
Poor feeding
Mottling of the skin.
Signs:
Hypoxemia refractory to supplemental oxygen
Pre- and post-ductal oxygen saturation difference greater than 10-15%
A prominent P2 heart sound
Murmur of a patent ductus arteriosus (PDA) or tricuspid regurgitation may be present
Signs of shock.
Diagnostic Criteria:
Clinical suspicion based on symptoms and signs
Confirmed by echocardiography demonstrating right-to-left shunting across the foramen ovale or ductus arteriosus and elevated pulmonary artery pressures
Arterial blood gas analysis showing significant hypoxemia (PaO2 < 60 mmHg) despite adequate inspired oxygen concentration.
Diagnostic Approach
History Taking:
Detailed maternal and perinatal history, including risk factors for PPHN such as infection, asphyxia, meconium staining, or congenital anomalies
Gestational age at birth
Mode of delivery
APGAR scores
Use of medications during pregnancy
History of congenital heart disease.
Physical Examination:
Complete cardiopulmonary examination, focusing on respiratory effort, breath sounds, presence of murmurs, and character of pulses
Assessment of peripheral perfusion and skin temperature
Measurement of pre- and post-ductal oxygen saturations
Evaluation for signs of shock.
Investigations:
Arterial blood gas analysis to assess oxygenation and ventilation
Chest X-ray to evaluate for underlying lung pathology (e.g., meconium aspiration syndrome, pneumonia) or diaphragmatic hernia
Echocardiography is the gold standard for diagnosing PPHN, assessing pulmonary artery pressure, identifying shunting, and evaluating cardiac function
Complete blood count, blood cultures if sepsis is suspected
Serum electrolytes and glucose.
Differential Diagnosis:
Congenital heart disease (especially those with increased pulmonary blood flow and cyanosis)
Sepsis with hypotension
Respiratory distress syndrome (RDS)
Pneumonia
Pulmonary hypoplasia
Transient tachypnea of the newborn (TTN)
Diaphragmatic hernia.
Management
Initial Management:
Provide adequate oxygenation and ventilation
Support systemic blood pressure with fluids and vasopressors if necessary
Minimize metabolic demand and stress
Maintain normothermia
Correct metabolic acidosis and hypocalcemia
Judicious use of sedatives.
Medical Management:
Inhaled Nitric Oxide (iNO): A selective pulmonary vasodilator
Typically initiated at 20 ppm and titrated based on response
Reduces pulmonary vascular resistance and improves oxygenation
Sildenafil: An oral or IV phosphodiesterase-5 (PDE5) inhibitor
Acts as a pulmonary vasodilator by increasing cyclic guanosine monophosphate (cGMP)
Dosing varies, often starting at 1-2 mg/kg per dose every 6-8 hours
Less rapid onset than iNO
May be used as an adjunct or alternative to iNO
Other vasodilators like milrinone or prostaglandins may be considered in specific situations
Supportive therapies for underlying causes (e.g., antibiotics for pneumonia).
Comparative Therapy Considerations:
iNO offers rapid and targeted pulmonary vasodilation with minimal systemic side effects, but is expensive and requires specialized equipment
Sildenafil is more accessible, can be administered orally or IV, and has systemic effects, but its onset is slower and may cause systemic vasodilation and hypotension
Current guidelines suggest iNO as first-line therapy in moderate to severe PPHN, with sildenafil as a second-line agent or adjunct
Evidence for early sildenafil use in MAS is growing.
Supportive Care:
Close monitoring of vital signs, oxygen saturation, and blood gases
Echocardiographic monitoring to assess response and monitor for complications
Nutritional support
Skin care to prevent breakdown
Early consultation with neonatology and pediatric cardiology teams.
Complications
Early Complications:
Hypoxemic crises
Recurrent shunting across PDA and foramen ovale
Systemic hypotension and shock
Renal compromise
Gastrointestinal dysfunction (necrotizing enterocolitis)
Seizures
Cerebral injury.
Late Complications:
Chronic lung disease of infancy
Pulmonary hypertension with growth restriction of pulmonary arteries
Neurodevelopmental deficits
Hearing impairment.
Prevention Strategies:
Prompt recognition and management of underlying causes
Judicious use of oxygen and mechanical ventilation
Avoidance of acidosis, hypothermia, and hypoglycemia
Early initiation of appropriate medical therapy for PPHN.
Prognosis
Factors Affecting Prognosis:
Severity of PPHN and degree of hypoxemia
Presence and severity of underlying condition (e.g., congenital diaphragmatic hernia, MAS)
Promptness and adequacy of treatment
Development of complications
Gestational age at birth.
Outcomes:
With optimal management, mortality rates have significantly decreased
Survivors may experience long-term sequelae such as chronic lung disease, neurodevelopmental delay, and hearing deficits
The prognosis is generally better for PPHN due to reversible causes than for PPHN associated with severe structural anomalies.
Follow Up:
Regular follow-up with a multidisciplinary team including neonatologists, pediatric cardiologists, pulmonologists, and developmental specialists
Serial echocardiograms to monitor pulmonary artery pressures and cardiac function
Neurodevelopmental assessments
Hearing screening.
Key Points
Exam Focus:
Understand the pathophysiology of PPHN including the role of prostaglandins, endothelin, and nitric oxide pathways
Differentiate between causes of PPHN and their specific management implications
Know the indications, dosages, and side effects of iNO and sildenafil
Recognize echocardiographic findings of PPHN
Understand the importance of pre- and post-ductal saturation monitoring.
Clinical Pearls:
iNO works by increasing cGMP in pulmonary vascular smooth muscle, leading to vasodilation
Sildenafil inhibits PDE5, preventing the breakdown of cGMP and promoting vasodilation
Always consider the underlying etiology of PPHN as this dictates specific management strategies
Differentiate PPHN from primary cardiac causes of cyanosis.
Common Mistakes:
Failure to promptly identify PPHN
Delaying treatment with vasodilators
Over-reliance on oxygen alone for refractory hypoxemia
Incorrect interpretation of echocardiography findings
Inadequate management of underlying conditions
Administering iNO without adequate ventilation support.