Pulmonary Hypertension of the Newborn
Clinical Practice Committee
Infants with Persistent Pulmonary
Hypertension of the Newborn (PPHN) are exceptionally unstable and difficult to
manage. After initial resuscitation the management should always be discussed
with the consultant on call.
Pulmonary hypertension of the newborn occurs in a variety of clinical
situations.1 These include meconium aspiration syndrome, hypoplastic
lungs, transient tachypnoea of the newborn, congenital pneumonia and hyaline
membrane disease. Secondary disturbances such as polycythaemia and myocardial
failure are contributory. There is frequently a history of chronic in utero
hypoxia, but some cases remain idiopathic.
- Pulmonary vasoconstriction is exacerbated by hypoxia and acidosis.
Meconium may trigger a vasoactive process to exacerbate this.
- Structural lung abnormalities (e.g. Congenital Diaphragmatic Hernia,
Congenital Pulmonary Airway Malformations, Alveolar Capillary Dysplasia) are
frequently associated with PPHN.
- Group B streptococcal sepsis
via Strep polysaccharide toxins.
- Polycythaemia, hyaline
membrane disease, hypocalcaemia and hypoglycaemia may contribute similarly.
- Some maternal medications e.g. NSAIDs, SSRIs 2
- This is essentially one of
exclusion of significant cyanotic congenital heart disease and severe
parenchymal lung disease. However, PPHN may coexist with significant
parenchymal lung disease.
- Have a high index of
suspicion for the '"at risk' group" in a term baby with respiratory distress
and cyanosis, particularly if there has been a history of intrauterine
hypoxia and meconium exposure or birth asphyxia.
Necessary investigations include
- serial arterial blood gases (simultaneous pre- and post-ductal samples may be helpful)
- full blood count
- blood cultures
- blood glucose
- chest radiograph
This is crucial to exclude cyanotic congenital heart disease (particularly
transposition of the great arteries, and totally anomalous pulmonary venous
return). In the presence of significant parenchymal lung disease,
cardiac assessment is less urgent.
Echocardiography is also useful to
- assess myocardial function, which is often severely affected
- assess the severity of PPHN, and assess responses to treatment.
- Tricuspid regurgitation - allows indirect measurement of the RV pressure and
- Ductual shunting
- Shunting through the foramen ovale
- Click here to see echocardiographic images of PPHN
- The hyperoxic test may play a role in diagnosis if 2D echocardiography is not available. However, severe
PPHN is likely to produce a similar result to cyanotic CHD.
Aims of Management
- Lower pulmonary vascular resistance.
- Maintain systemic blood pressure.
- Reverse right-to-left shunting.
- Improve arteriolar oxygen saturation and oxygen delivery to the tissues.
- Minimise barotrauma.
1. Oxygen and ventilation
- 100% O2
Always start with 100% oxygen
and reduce the FiO2, rather than starting on 25% and increasing.
In the short term there is no risk to a term baby using such measures.
- Normo-ventilation i.e. pO2 7-12 kpa is acceptable if baby stable
- pCO2 5-7 kpa if this can be achieved
- Use of HFOV, particularly in combination with inhaled Nitric Oxide, has been shown to reduce the
need for ECMO.
2. Pulmonary vasodilators
- Inhaled nitric oxide (iNO) is the vasodilator of choice.
iNO should be started at 20ppm and reduced to 5ppm as able, according to
response and to stability.
Methaemoglobin levels should be monitored (these are measured
automatically on blood gases).
Nitrogen dioxide (NO2) levels should be monitored and kept
- Sildenafil has been reported to reduce mortality where in
centres where iNO/ECMO is not available. It improves oxygenation and may
be helpful in the prevention of rebound pulmonary hypertension. 4,5
Milrinone has inotropic
and vasodilator effects and is used in neonatal patients post cardiac
surgery. Two small case reports reported improved oxygenation. 6.7
(It is rarely used in ACH.)
Magnesium sulphate may be
used in refractory cases. The use of MgSO4 is
controversial but may be indicated in selected instances.
- Prostacyclin may also be
used in severe and refractory cases, although it is difficult to obtain
and its use is controversial.
- Tolazoline is no longer
used at ACH. It is a non-registered medication. It has an
unpredictable effect and frequently results in systemic hypotension and
- Myocardial function is frequently poor, despite reasonable blood
- Aim to keep the mean arterial pressures above 50mm Hg in term infants
or higher if RV pressure calculated to be greater than this.
- Use volume (initially normal saline) and inotropic support: dopamine
and / or dobutamine, both starting at 5-10 mcg/kg/min. If the systemic
pressure increases and pulmonary pressure stays the same, R-L shunt will
- Adrenaline infusions may be indicated if there is severe myocardial dysfunction
- Many babies are very unstable requiring early use of narcotic
- A ‘minimal handling’ approach should also be used. 1
5. Muscle Relaxation
- This may be necessary to gain initial control in very vigorous babies who are not adequately
sedated with narcotics and are fighting the ventilator to their detriment.
- Use pancuronium 100micrograms/kg/dose PRN preferably for 24 hours or less.
- Monitor for possible associated systemic hypotension; some babies
may require additional fluid volume support.
6. Avoid polycythaemia
- Aim to keep the PCV between 0.40 and 0.45.
- Establish the critical pH- preferably 7.45 but may be higher. If there is no dramatic
improvement in PaO2 at a pH >7.6, the infant can be deemed to be
- Use small boluses of
bicarbonate (1-2 mmol/kg) or
a continuous infusion (0.5mmol/kg/hour
initially). Liberal bicarbonate use may result in hypernatraemia
- Inducing alkalosis by hyperventilation often
creates as many problems as it solves and is no longer
- This is essentially prolonged cardio-pulmonary bypass and is provided via PICU at Starship
- Usual criteria are infants who have an
Oxygenation Index (OI) >30.
- It is
appropriate to discuss infants who may potentially require ECMO with the
PICU specialist early, rather than when ECMO or death are
imminent. This will be done specialist-to-specialist. The
neurological status of the infant may be an important factor in
determining if ECMO is offered.
where MAP is Mean Airway
PaO2 is the arterial oxygen tension in mmHg (1kPa = 7.5mmHg), and
FiO2 is the fraction of inspired oxygen (100% = 1.0, air = 0.21)
- Pay careful attention to maintaining normal electrolyte,
blood glucose and calcium concentrations and to baby’s
- In meconium aspiration syndrome associated PPHN some
babies may benefit from surfactant bolus or intravenous
- In babies on long term ventilation, particularly if they
are growth restricted from the outset, intravenous nutrition
may be required.
- Weaning such babies is invariably difficult. Steps should be taken one at a time and by small increments once lability appears to have stabilised.
Roberton’s Textbook of Neonatology. Ed JM
Rennie. Elsevier, 2005. ISBN 0-44307-355-4.
Kieler H, Artama M, Engeland A et al
Selective serotonin reuptake inhibitors during pregnancy and risk of
persistent pulmonary hypertension in the newborn: population based
cohort study from the five Nordic countries. BMJ. 2012 Jan 12;344:d8012.
Finer NN, Barrington KJ. Nitric oxide for
respiratory failure in infants born at or near term. Cochrane Database
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Steinhorn RH, Kinsella JP, Pierce C,et
al.. Intravenous sildenafil in the treatment of neonates with persistent
pulmonary hypertension. J Pediatr. 2009 Dec;155(6):841-847
Baquero H, Soliz A, Neira F, et al. Oral
sildenafil in infants with persistent pulmonary hypertension of the
newborn: a pilot randomized blinded study. Pediatrics. 2006
Bassler D, Choong K, McNamara P, Kirpalani
H. Neonatal persistent pulmonary hypertension treated with milrinone:
four case reports. Biol Neonate. 2006;89(1):1-5
McNamara PJ, Laique F, Muang-In S, Whyte
HE. Milrinone improves oxygenation in neonates with severe persistent
pulmonary hypertension of the newborn.J Crit Care. 2006