The aim of this pilot randomized controlled blinded study is to evaluate the feasibility of using nebulized magnesium sulfate in the treatment of PPHN.

The effectiveness and safety of nebulized magnesium sulfate (using isotonic solution in a dose of 1024 mg/hour) is compared with intravenous magnesium sulfate (200 mg/kg over 30 minutes, followed by 50 mg/kg/hour) in treating mechanically ventilated neonates with severe persistent pulmonary hypertension of the newborn.

Inclusion Criteria:

Newborns with PPHN fulfilling the following:

1. born at ≥ 37 weeks gestational age.
2. birth weight between 2.5 and 4 kg.
3. post-natal age between 6 and 72 hours.
4. connected to mechanical ventilation with an oxygenation index (OI) > 30 on two occasions at least 15 minutes apart.
5. documented PPHN confirmed by echocardiography.

Exclusion Criteria:

1. failure to obtain informed consent.
2. infants of mothers who received magnesium sulfate within 48 hours before labor.
3. congenital heart diseases (other than PDA and foramen ovale).
4. major congenital anomalies (including congenital diaphragmatic hernia and lung hypoplasia).
5. prior need for cardiopulmonary resuscitation.
6. mean arterial blood pressure (MABP) < 35 mmHg despite therapy with volume infusions and inotrpic support.
7. impaired kidney function.
8. prior administration of pulmonary vasodilators.

Each neonate was assigned a unique identification number. Pharmacy filled the active and placebo preparations in similar containers with sealed code for identification. Participants' families, treating clinicians, nurses, echocardiographers, and data collectors were unaware of group assignment and drug/placebo therapy.