Treatment of Persistent Pulmonary Hypertension in Neonates With Nebulized Magnesium Sulfate

Phase 2

Completed

Interventions: Drug: Inhalational magnesium sulfate
Drug: IV Magnesium Sulfate

Brief Summary: we conducted this study to compare between effect of nebulized and intravenous magnesium sulfate (MgSO₄) for better treatment of persistent pulmonary hypertension of neonates with less side effects.

Detailed Description: Persistent pulmonary hypertension of the newborn (PPHN) is a serious syndrome characterized by sustained fetal elevation of pulmonary vascular resistance (PVR) at birth. The syndrome is seen in two of 1000 live-born infants and is associated with anormal or low systemic vascular resistance. Pulmonary hypertension is defined as a mean pulmonary artery pressure greater than 25 mmHg at rest and \> 30 mmHg during exercise. PPHN-targeted therapy is used for infants with PPHN who fail to respond to general cardiopulmonary supportive care. Oxygen and inhaled Nitric Oxide (iNO) are the only well-studied pulmonary vasodilators in neonates with PPHN. Magnesium is a potent vasodilator and hence has the potential to reduce the high pulmonary arterial pressures as it's able to dilate constricted muscles in the pulmonary arteries. However, its action is not specific and when given via an intravenous infusion, it will act on other muscles in the body including other arteries. Excessive magnesium causes hypotonia, hypotension, and cardiorespiratory failure. However, no studies have demonstrated long-term benefit. Delivering magnesium sulfate by nebulization may enhance effectiveness and minimizes systemic adverse effects.

Recruitment & Eligibility

Inclusion Criteria

Newborns with documented persistent pulmonary hypertension as confirmed by echocardiography.
Neonates born at ≥ 35 wk. gestation with a birth weight of 2.5-4 kg
Neonates have to be connected to mechanical ventilation with an oxygenation index (OI) >30 on two occasions at least 15 min apart.
The echocardiogram had to show a predominant right-to-left or bidirectional shunt (through ductus arteriosus and/or foramen oval) and/or tricuspid regurgitant jet with a pressure gradient ≥ 2/3 of the systemic systolic blood pressure.

Exclusion Criteria

Infants of parents who refuse to give informed consent.
Infants of mothers who receive magnesium sulfate within 48 h before labor.
Congenital heart diseases other than patent ductus arteriosus (PDA) and foramen ovale.
Major congenital anomalies, including congenital diaphragmatic hernia and lung hypoplasia.
Prior need for cardiopulmonary resuscitation
Mean arterial blood pressure (MABP) < 35 mmHg despite therapy with volume infusions and vasoactive inotropes.
Impaired kidney function; and prior administration of pulmonary vasodilators or prior administration of surfactant.

Arm && Interventions

Group	Intervention	Description
Nebulized magnesium (NebMag) group 1	Inhalational magnesium sulfate	NebMag group (n=20) was administered nebulized isotonic magnesium (64 mg/mL). For nebulization, an isotonic MgSO₄ solution (64 mg/mL) was formulated by diluting a 10% intravenous preparation of MgSO₄ heptahydrate with sterile distilled water. 4 mL aliquots of the isotonic MgSO₄ solution (containing 256 mg of MgSO₄) were administered every 15 minutes through the jet nebulizer connected to the ventilator during the 24 hour study period.
Intravenous magnesium (IVMag) group 2	IV Magnesium Sulfate	IVMag group (n=20) received intravenous magnesium. For intravenous administration, a 10% MgSO₄ solution was prepared by diluting a 50% intravenous formulation of MgSO₄ heptahydrate with 5% glucose and administrated in a loading dose of 2 mL/kg over 30 minutes (equivalent to 200 mg/kg of MgSO₄), followed by a continuous infusion at a rate of 0.5 mL/kg/h (equivalent to 50 mg/kg/h of MgSO₄) over the 24 hour study period.

Primary Outcome Measures

Name	Time	Method
Mean Airway Pressure (cm H2O)	from baseline to 12 and 24 hours after administering the study drug
Fraction of Inspired Oxygen (FiO2) (%)	from baseline to 12 and 24 hours after administering the study drug
PaO2 (mmHg)	from baseline to 6, 12 and 24 hours after administering the study drug	kPa x 7.5 converts to the equivalent PaO2 in mmHg
Tracking Changes in the Oxygenation Index (OI)	from baseline to 12 and 24 hours after administering the study drug	OI evaluates both oxygenation and ventilatory support, aiding decisions on Extracorporeal Membrane Oxygenation (ECMO) necessity in newborns with PPHN. OI calculated as (Mean Airway Pressure (cm H2O) x Fraction of Inspired Oxygen (%) x 100) ÷ (PaO2 (kPa) x 7.5). OI is routinely used as an indicator of severity of hypoxemic respiratory failure (HRF) in neonates, with an arbitrary cutoff of 15 or less for mild HRF, between 16 and 25 for moderate HRF, between 26 and 40 for severe HRF, and more than 40 for very severe HRF

Secondary Outcome Measures

Name	Time	Method
the Variations in Mean Arterial Blood Pressure (MABP)	at 0, 12, and 24 hours post administration of the study drug relative to baseline	Both systolic and diastolic pressure are used to calculate MABP.
the Alterations in Serum Magnesium Levels (mmol/L)	from baseline to 12 hours following the administration of the study drug.