PPHN Persistent Pulmonary Hypertension of the Newborn

Full article available here.

Pulmonary hypertension of the newborn with right to left shunt occurs in a variety of clinical situations. 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.

Pathogenesis

• Pulmonary vasoconstriction is exacerbated by hypoxia, acidosis, and hypercapnia (secondary to changes in pH). Meconium may trigger vasoactive process to exacerbate this.
• Anatomic abnormality of the pulmonary vascular bed (e.g. pulmonary hypoplasia with pulmonary arteriolar smooth muscle hypertrophy) or chronic in-utero hypotension following chronic intrauterine hypoxia may also play a role.
• Birth asphyxia with hypoxia, acidosis and shock is clinically associated with increased responsivity of the pulmonary vascular bed.
• Group B streptococcal sepsis via Strep polysaccharide toxins.
• Polycythaemia, hyaline membrane disease, hypocalcaemia and hypoglycaemia may contribute similarly.
• Structural lung abnormalities (e.g. congenital diaphragmatic hernia, CCAM, ...) are frequently associated with PPHN.

Diagnosis

• 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.

Tests

Necessary tests may include

• chest xray
• serial arterial blood gases (simultaneous pre- and post-ductal samples may be helpful)
• full blood count
• blood cultures
• blood glucose
• calcium
• Echocardiogram.
  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
  1. assess myocardial function, which is often severely affected
  2. assess the severity of PPHN, and assess responses to treatment.
     • Tricuspid regurgitation - allows indirect measurement of the RV pressure and therefore severity
     • Ductual shunting
     • Shunting through the foramen ovale
• 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

1. Lower pulmonary vascular resistance.
2. Maintain systemic blood pressure.
3. Reverse right-to-left shunting.
4. Improve arteriolar oxygen saturation and oxygen delivery to the tissues.
5. Minimize barotrauma.

Specific Therapies

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. Normotension	Myocardial function is frequently poor, despite reasonable blood pressures. Aim to keep the mean arterial pressures above 50mm Hg in term infants Use volume (initially normal saline) and dopamine -starting with 5-10 mcg/kg/min and/or dobutamine 5-10 mcg/kg/min if systemic pressure raises and pulmonary pressure stays the same, R-L shunt will diminish . Adrenaline infusions may be indicated if there is severe myocardial dysfunction
3. Avoid polycythaemia	Aim to keep the PCV between 0.40 and 0.45.
4. Alkalosis	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 "pH unresponsive". 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 and hypokalaemia.
5. Sedation	Many babies are very unstable. Consider early use of narcotic infusions.
6. 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.
7. 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 below 1ppm. Magnesium Sulfate 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.
8. Hyperventilation	Inducing alkalosis by hyperventilation often creates as many problems as it solves and is best avoided. There can be an improvement in PO2.
10. Weaning	Weaning such babies is invariably difficult. Steps should be taken one at a time and by small increments once lability appears to have stabilized.

11. Ecmo

Prolonged cardio-pulmonary bypass with usual criteria of infants who have an Oxygenation Index of less than 40.