Introduction
Persistent pulmonary hypertension of the newborn (PPHN) is a clinical
syndrome characterized by the presence of respiratory failure and
hypoxia. PPHN develops if pulmonary vascular resistance exceeds the
systemic vascular resistance for a prolonged time after birth. This
leads to right-to-left shunting of hypo-oxygenated blood through the
foramen ovale (F.o.) and, in most cases also through persistent ductus
arteriosus (DA) [1]. A consequence of this is severe hypoxemia
associated with the presence of a substantial proportion of
hypo-oxygenated venous blood in the systemic circulation [2].
The prevalence of PPHN is estimated at 0.4-6.8 ‰ of live births [3].
Although PPHN is observed primarily in full-term neonates or those
delivered nearly at term, it may also be diagnosed in some preterm
newborns with respiratory disorders and bronchopulmonary dysplasia.
Typically, PPHN develops secondary to delayed or impaired pulmonary
vascular relaxation, associated with various lung pathologies [4].
The causes of PPHN can be classified into the four groups: 1)
developmental malformations (pulmonary hypoplasia, congenital
diaphragmatic hernia, Potter syndrome, alveolar capillary dysplasia), 2)
anatomical changes in pulmonary vessels (chronic intrauterine hypoxia,
salicylate ingestion in pregnancy, smoking in pregnancy), 3) pulmonary
vasoconstriction (congenital pneumonia, meconium aspiration syndrome,
severe perinatal hypoxia, sepsis, respiratory distress syndrome), and 4)
disorders of the pulmonary circulation (pulmonary embolism,
polycythemia) [5].
Currently, the gold standard in the management of PPHN is inhaled nitric
oxide (iNO), and the most advanced treatment option is extracorporeal
membrane oxygenation (ECMO). However, in line with the proposed Polish
standards of PPHN management, alternative treatment modalities can be
used whenever iNO therapy is unavailable or contraindicated [6].
Contraindications to iNO therapy include intraventricular hemorrhage
(IVH, more than grade 2), severe disorders of hemostasis (unless
compensated), >5% methemoglobinemia and deficiency of
hemoglobin reductase. The iNO product available in Poland has not been
authorized for the use in neonates born before 34 weeks of gestation
[7]. The list of proposed alternative treatment modalities includes
magnesium sulfate, milrinone and sildenafil.
In this paper, we review three cases of severe PPHN, all initially
treated with magnesium sulfate. Given the lack of adequate treatment
response, the patients were switched to milrinone (Corotrope),
administered according to the product dossier. The severity of
respiratory failure was estimated based on oxygen saturation index (OSI)
which despite being less invasive measure than oxygenation index (OI)
(contrary to OI, determination of OSI does not require arterial access)
was shown to correlate well with the latter (OI ≈ 2 × OSI) [8-10].