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Key messages

  • Diagnosis of persistent pulmonary hypertension (PPHN) should be confirmed by cardiac echo as soon as feasible.
  • Early consultation with PIPER is advisable.
  • Maintain adequate systemic BP with inotropes if required.
  • Nitric oxide is safe and usually effective in PPHN up to a dose of 20 ppm.
  • Minimise handling the infant.
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    Please note that some guidelines may be past their review date. The review process is currently paused. It is recommended that you also refer to more contemporaneous evidence.

    Persistent pulmonary hypertension (PPHN) is when the neonate fails to make the transition from fetal circulation to normal newborn circulation.

    One of the main challenges facing a neonate making the transition to the extra-uterine environment is that of cardiopulmonary adaptation.

    Central to this process is a dramatic drop in pulmonary vascular resistance due to a number of influences including:

    • lung inflation
    • increased oxygen levels in the blood
    • vascular endothelial factors including nitric oxide.

    Delayed relaxation of the pulmonary vascular bed and consequent PPHN is seen in association with many neonatal respiratory diseases including:

    The syndrome may also be seen in the absence of triggering diseases.

    Right to left shunting across the ductus arteriosus and foramen ovale characterises PPHN, hence the alternate name ‘persistent fetal circulation’.

    A ‘vicious cycle’ of worsening hypoxia causing increasing pulmonary vascular resistance, in turn reducing oxygen uptake provides a substantial therapeutic challenge.

    Differential diagnosis

    Differential diagnosis for persistent pulmonary hypertension involves the following:

    • Structural heart disease needs to be excluded when PPHN is considered a likely diagnosis.
    • Echocardiography is the definitive diagnostic tool but is not always available.
    • Clinical examination is of limited value. A single second heart sound is present in many cyanotic heart defects and clinical or radiological evidence of cardiac failure suggests structural cardiac disease.
    • The use of pre-ductal and post-ductal oxygen saturations to make the diagnosis of PPHN is readily available but has limitations. Normal right arm oxygen saturations with low oxygen saturations on the left arm/lower limb are the classic finding but may not be present if right to left shunting is prominent.
    • The combination of patent ductus arteriosus (PDA) with coarctation of the aorta may produce differential cyanosis, mimicking PPHN.
    • The clinical course of the disease and response to therapy may be the most useful diagnostic tool particularly where resources are limited.

    Investigations

    Investigation may include:

    • chest x-ray
    • echocardiography
    • doppler studies of ductal and tricuspid regurgitation in conjunction with simultaneous blood pressure measurements provide an accurate indication of right-sided cardiac pressures and physiology.
    • cerebral ultrasound.

    Management

    The primary goal of therapy is to selectively reduce pulmonary vascular resistance and thereby improve oxygenation.

    Special care nursery management

    SCN management involves:

    • oxygen with or without respiratory support
    • venous access - IV or UV
    • correction of hypoglycaemia and acidosis
    • checking Ca and Mg, correct if levels are low
    • maintaining neutral thermal environment
    • minimising handling
    • early consultation with PIPER regarding:
      • need to transfer
      • respiratory support
      • diagnosis/differential diagnosis
      • tertiary management advice  
    • urgent echocardiogram (if available) to exclude cyanotic congenital heart disease (where Prostin infusion may be life saving)
    • commence Prostin infusion if suspected cyanotic congenital heart disease and unable to obtain urgent echocardiogram.

    Neonatal intensive care unit management

    Nitric oxide is the only specific therapy shown to reduce pulmonary vascular resistance.

    Other appropriate management strategies depend on the underlying disease process and include the following:

    • Provide liberal supplemental oxygen.  
    • Give exogenous surfactant if surfactant deficiency is present.
    • High-frequency ventilation is frequently used in PPHN.
    • Use bicarbonate judiciously. Do not administer unless there is adequate assisted ventilation.
    • Muscle relaxation with pancuronium and liberal use of sedation (such as morphine) may assist in achieving adequate ventilation.
    • Minimal handling is best.
    • Support systemic blood pressure with inotropes such as dopamine and dobutamine.
    • Extracorporeal membrane oxygenation (ECMO) may be required.

    Once adequate oxygenation is achieved, weaning of oxygen and other ventilator settings should be done slowly. Frequently oxygenation will decrease suddenly and dramatically after small decreases in FiO2 or ventilator settings and may take several hours to recover.

    Areas of uncertainty in clinical practice

    Therapies for PPHN are largely untested in randomised controlled trials and many controversies about management strategies remain.

    More information

    Clinical

    References

    • Kinsella JP, Abman SH. Recent developments in the pathophysiology and treatment of persistent pulmonary hypertension of the newborn. J Pediatr 1995; 126:853-864.
    • Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term (Cochrane Review). Cochrane Database Syst Rev 1902; 4:CD000399

    Other reading

    • Zahka KG and Chandrakant RP. Cardiac problems of the neonate. In Fanaroff and Martin (eds) Neonatal-Perinatal Medicine: diseases of the fetus and infant
    • Shah PS, Ohlsson A. Sildenafil for pulmonary hypertension in neonates. Cochrane Database of Systematic Reviews 2011, Issue 8. Art. No.: CD005494. DOI: 10.1002/14651858.CD005494.pub3

    Get in touch

    Clinical Guidance Team
    Safer Care Victoria

    Version history

    First published: August 2013
    Review by: August 2016

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