Nebulized Magnesium Sulfate for Treatment of Persistent Pulmonary Hypertension of Newborn: A Pilot Randomized Controlled Trial

Abstract

Objectives: To investigate the effectiveness of nebulized magnesium sulfate in treating persistent pulmonary hypertension of newborn (PPHN).

Methods: Twenty-eight mechanically ventilated term neonates with severe PPHN were randomized into two groups: NebMag group (n = 14), who receiving nebulized isotonic magnesium (1024 mg/h), and IVMag group (n = 14), who received intravenous magnesium (200 mg/kg over 30 min, followed by 50 mg/kg/h). The study time frame was 24 h. Outcome measures were the changes in oxygenation index (OI), mean arterial blood pressure (MABP), vasoactive inotropic score (VIS), and serum magnesium level.

Results: Baseline demographic, ventilatory, and hemodynamic characteristics were comparable between the two groups. At the end of the study, the OI decreased by 44.3% in the NebMag group compared with 35.3% in the IVMag group (mean difference -3.14; 95%CI -5.08, -1.19; p 0.003). The NebMag group had a higher MABP (mean difference 2.29 mmHg; 95% CI 1.80, 2.77; p 0.000) and lower VIS (mean difference -14.64; 95% CI -16.52, -12.77; p 0.000) at the 24-h study time point. The increase in serum magnesium level, measured at 12-h study time point, was lower in the NebMag group (mean difference -2.26 mmol/L; 95% CI -2.58, -1.96; p 0.000).

Conclusion: Nebulized magnesium sulfate may be an effective therapeutic modality for neonates with severe PPHN on mechanical ventilation, but this should be confirmed by larger studies. Retrospectively registered at www.clinicaltrials.gov (identifier: NCT04328636).

Keywords: Hypoxia; Magnesium; Nebulizer; Neonate; PPHN; Persistent fetal circulation.

Fig. 1

Flowchart of study enrollment

Fig. 2

Changes in oxygenation index (OI). Following study drug administration, the nebulized magnesium group had lower measures of OI than the intravenous magnesium group. The difference in OI between groups increased by time and became statistically significant only at the 24-h study time point (2-h, p = 0.458; 6-h p = 0.176; 12-h, p = 0.051; 24-h, p = 0.003)

Fig. 3

Changes in mean arterial blood pressure and vasoactive inotropic score. Following study drug administration, the nebulized magnesium group had higher mean arterial blood pressure (MABP) and lower vasoactive inotropic score (VIS) than the intravenous magnesium group. The differences in MABP and VIS between the two groups were statistically significant (p = 0.000) at the 2-, 6-, 12-, and 24-h study time points