Treatment of Persistent Pulmonary Hypertension in Neonates With Nebulized Magnesium Sulfate (PPHN)

Benha University

Status and phase: Completed; Phase 3; Phase 2

Conditions: Magnesium Sulfate - PPHN

Treatments: Drug: Inhalational magnesium sulfate; Drug: IV Magnesium Sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT06603766

39-9-204

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 1 hour to 3 days old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

40 participants in 2 patient groups

Nebulized magnesium (NebMag) group 1

Active Comparator group

Description:

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.

Treatment:

Drug: Inhalational magnesium sulfate

Intravenous magnesium (IVMag) group 2

Active Comparator group

Description:

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.

Treatment:

Drug: IV Magnesium Sulfate