Purpose and Goal: CNEP # 2043

  • Describe the pathophysiology of persistent pulmonary hypertension in the newborn.
  • Identify at least two strategies for the treatment of persistent pulmonary hypertension in the newborn.

None of the planners, faculty or content specialists has any conflict of interest or will be presenting any off-label product use. This presentation has no commercial support or sponsorship, nor is it co-sponsored.

Requirements for successful completion:

  • Successfully complete the post-test
  • Complete the evaluation form


  • October 2015 – October 2017

Learning Objectives

  • Describe the pathophysiology of persistent pulmonary hypertension in the newborn.
  • Describe the clinical presentation of persistent pulmonary hypertension in the newborn.
  • Describe at least two strategies for the treatment of persistent pulmonary hypertension in the newborn.


  • Persistent Pulmonary Hypertension is also known as PPHN
  • PPHN was previously known as Persistent Fetal Circulation
  • PPHN is a major clinical problem in the NICU
  • It is caused by a failed transition to extra-uterine life
  • PPHN primarily affects infants born later than 34 weeks gestation

Persistent Pulmonary Hypertension

  • PPHN occurs in as many as 7 out of 1000 births
  • Presents as hypoxemic respiratory failure
    • Results from poor hemodynamic transition
    • Results from poor respiratory transition
  • It can lead to significant morbidity and mortality
  • The mortality rate is as high as 20%

Pathophysiology of PPHN

  • Occurs when pulmonary vascular resistance is elevated
  • In-utero fetal circulation
    • Pulmonary vascular resistance is high
    • In-utero shunts move blood away from the lungs
    • Less than 10% of blood volume circulates to the lungs
  • At birth, pulmonary vascular resistance should rapidly decrease
    • In-utero shunts constrict
    • Blood and oxygen flow freely to the lungs
  • In PPHN, pulmonary vascular resistance fails to decrease
  • In-utero shunts remain open
    • Patent foramen ovale (PFO)
    • Patent ductus arteriosus (PDA)
  • The majority of cardiac output is shunted away from the lungs
  • Failure to transition results in severe systemic hypoxemia

Causes or Categories of PPHN

  • Parenchymal lung disease
    • Meconium aspiration syndrome
      • Most common cause of PPHN
    • Respiratory distress syndrome
    • Pneumonia
    • Sepsis
  • Idiopathic
    • Structural abnormalities
  • Pulmonary hypoplasia
    • Congenital diaphragmatic hernia
    • Cystic adenomatoid malformation
    • Renal agenesis

Clinical Presentation

  • Prenatal risks factors:
    • Intrauterine and perinatal depression
    • Fetal heart rate abnormalities
    • Meconium staining
  • PPHN presents as respiratory distress
    • Tachypnea
    • Retractions
    • Grunting
    • Cyanosis
  • PPHN should be suspected in any infant with hypoxemia
    • PaO2 remains < 55% despite 100% FiO2
  • Pre-ductal oxygen saturations (right hand) are higher
  • Post-ductal oxygen saturations (left hand or leg) are lower
  • Definitive diagnosis is via Echocardiogram
    • Assess right-to-left shunting through the PDA
    • Assess presence of tricuspid regurgitation
    • Assess the presence of arterial septum bowing
    • Assess pulmonary artery pressures
    • Evaluate for cardiac or pulmonary disease

Treatment Goals

  • The treatment goals for PPHN include:
    • Lower pulmonary vascular resistance
    • Reduce intra-cardiac shunting
    • Improve post-ductal oxygen saturations
    • Correct the underlying cause of PPHN
  • Supportive care to avoid pulmonary vasoconstriction
    • Correct temperature instability
    • Correct glucose abnormalities
    • Correct electrolyte abnormalities
    • Correct metabolic acidosis
    • Correct systemic hypotension

Treatment Strategies

  • Treat metabolic derangements
    • Correct acidosis
    • Correct hypoglycemia
    • Correct hypocalcemia
  • Optimize lung recruitment
    • Mechanical ventilation
    • High-Frequency ventilation (HFOV)
    • Surfactant replacement
  • Optimize cardiac output
    • Correct anemia from blood loss
    • Packed red blood cell replacement
  • Optimize left ventricular function
    • Dopamine
    • Dobutamine
    • Epinephrine
    • Milrinone
  • Pulmonary vasodilators
    • Inhaled nitric oxide
  • Future therapies
    • Phosphodiesterase inhibitors
      • Sildenafil

Assessment of Severity Using Oxygenation Index

  • The oxygen index (OI) is used to guide timing of interventions
  • A high OI indicates severe hypoxemic respiratory failure
    • Use of HFOV
    • Use of Nitric oxide
    • Use of ECMO
  • OI = (mean airway pressure x FiO2 ÷ PaO2) x 100
  • An OI > 25 indicates need for HFOV support
    • Nitric oxide and ECMO should be readily available
    • The infant should be transferred to an ECMO center
  • An IO < 25 indicates that supportive care may be adequate

Inhaled Nitric Oxide

  • Inhaled nitric oxide is also known as iNO
  • iNO is a selective pulmonary vasodilator
  • iNO improves oxygenation
    • Regulates pulmonary vascular tone
    • Decreases pulmonary arterial pressures
    • Redistributes blood flow to the lungs
  • Usual maximum dose is 20 ppm
    • Doses > 20 ppm have not been shown to be effective
  • iNO is typically required over a 3-4 day course
  • iNO has been shown to reduce the need for ECMO


  • Sildenafil is a phosphodiesterase inhibitor
  • It may be administered intravenously or enterally
    • Optimal doses differ with each
    • Optimal dosing has not been proven
  • Sildenafil reduces pulmonary vascular resistance
  • It significantly reduces rebound PPHN after iNO
  • It improves outcomes used alone or with iNO
  • Further research is needed before widespread use

Use of ECMO

  • ECMO is extra corporeal membrane oxygenation
    • It functions as a lung bypass
    • It maintains adequate tissue oxygenation
    • It avoids irreversible lung damage from ventilation
  • ECMO may be indicated for a persistent IO > 40
  • 40% of infants with PPHN require ECMO
  • ECMO is typically required for 7 days

Sedation and Therapeutic Management

  • Ventilated infants may become easily agitated
    • Especially if breathing out of synch with ventilator
  • Agitation may cause increased shunting
    • Shunting → increased pulmonary vascular resistance
    • Shunting → further hypoxemia and respiratory failure
  • An opioid drip may be required to avoid agitation
    • Morphine drip at 10-20 mcg/kg/hour
    • Fentanyl drip at 1-5 mcg/kg/hour
  • A neuromuscular paralytic may also be required

Supportive NICU Care

  • Infants with PPHN are especially sensitive to stimulation
  • Over stimulation leads to crying and hypoxemia
    • Crying → to an open PDA
    • An open PDA → to shunting
    • Shunting → to hypoxemia
  • Excessive noise and handing must be avoided
    • Minimal noise and light is critical
    • Minimal handling is critical
      • All exams should be coordinated
      • Care should be clustered as tolerated
      • Long quiet rest periods should be provided
  • Discomfort and agitation must be minimized
    • Minimal handling and stimulation is critical
    • Opioid drips should be standard care


  • PPHN occurs primarily in term or late preterm infants
  • PPHN should be considered in any infant with hypoxemia
  • The differential diagnoses of PPHN include:
    • Cyanotic congenital heart disease
    • Primary pulmonary disorders
    • Sepsis
  • Survivors of PPHN are at risk for:
    • Developmental delay
    • Motor disabilities
    • Hearing deficits
  • Supportive care is critical and should be initiated immediately
  • Infants with severe PPHN require transfer to an ECMO center


  1. Adams, J.M. & Stark, A.R. 2014. Persistent Pulmonary Hypertension in the Newborn. Up-To-Date.
  2. Verklan, M.T. 2006. Persistent Pulmonary Hypertension of the Newborn: Not a Honeymoon Anymore. Journal of Perinatal and Neonatal Nursing, 20 (1), p. 108-112.
  3. Steinhorn, R.H. & Farrow, K.N. 2007. Pulmonary Hypertension in the Neonate. NeoReviews, 8 (1), p. e14-e22.
  4. Spillers, J. 2010. PPHN: Is Sildenafil the New Nitric? A Review of the Literature. Advances in Neonatal Care, 10 (2), p. 69-74.


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