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

Elsayed Abdelkreem, Shaimaa M Mahmoud, Moustafa O Aboelez, Mohamed Abd El Aal, Elsayed Abdelkreem, Shaimaa M Mahmoud, Moustafa O Aboelez, Mohamed Abd El Aal

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.

Conflict of interest statement

None.

© 2021. Dr. K C Chaudhuri Foundation.

Figures

Fig. 1
Fig. 1
Flowchart of study enrollment
Fig. 2
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
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

References

    1. Mathew B, Lakshminrusimha S. Persistent pulmonary hypertension in the newborn. Children. 2017;4(8):63. doi: 10.3390/children4080063.
    1. Krishna MR, Kumar RK. Diagnosis and management of critical congenital heart diseases in the newborn. Indian J Pediatr. 2020;87(5):365–371. doi: 10.1007/s12098-019-03163-4.
    1. Lakshminrusimha S, Keszler M. Persistent pulmonary hypertension of the newborn. Neorev. 2015;16(12):e680–e692. doi: 10.1542/neo.16-12-e680.
    1. El-Khuffash A, McNamara PJ, Breatnach C, et al. The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1): study protocol and review of literature. Matern Heal Neonatol Perinatol. 2018;4(1):24. doi: 10.1186/s40748-018-0093-1.
    1. Lai M-Y, Chu S-M, Lakshminrusimha S, Lin H-C. Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Pediatr Neonatol. 2018;59(1):15–23. doi: 10.1016/j.pedneo.2016.09.011.
    1. Wedgwood S, Steinhorn RH, Lakshminrusimha S. Optimal oxygenation and role of free radicals in PPHN. Free Radic Biol Med. 2019;142:97–106. doi: 10.1016/j.freeradbiomed.2019.04.001.
    1. Nakwan N. The practical challenges of diagnosis and treatment options in persistent pulmonary hypertension of the newborn: a developing country’s perspective. Am J Perinatol. 2018;35(14):1366–1375. doi: 10.1055/s-0038-1660462.
    1. Chettri S, Bhat BV, Adhisivam B. Current concepts in the management of meconium aspiration syndrome. Indian J Pediatr. 2016;83(10):1125–1130. doi: 10.1007/s12098-016-2128-9.
    1. Kelly LE, Ohlsson A, Shah PS. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev. 2017;8(8):CD005494.
    1. Shivanna B, Gowda S, Welty SE, Barrington KJ, Pammi M. Prostanoids and their analogues for the treatment of pulmonary hypertension in neonates. Cochrane Database Syst Rev. 2019;10(10):CD012963.
    1. Ho JJ, Rasa G. Magnesium sulfate for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev. 2007;18(3):CD005588.
    1. Shaltout F, Hegazy R, Aboulghara H, Abdel ML. Magnesium sulphate versus sildenafil in the treatment of persistent pulmonary hypertension of the newborn. Int J Clin Pediatr. 2012;1(1):19–24.
    1. de Boode WP, Singh Y, Molnar Z, et al. Application of neonatologist performed echocardiography in the assessment and management of persistent pulmonary hypertension of the newborn. Pediatr Res. 2018;84(S1):68–77. doi: 10.1038/s41390-018-0082-0.
    1. Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, Charpie JR, Hirsch JC. Vasoactive–inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med. 2010;11(2):234–238. doi: 10.1097/PCC.0b013e3181b806fc.
    1. Hill NS, Preston IR, Roberts KE. Inhaled therapies for pulmonary hypertension. Respir Care. 2015;60(6):794–805. doi: 10.4187/respcare.03927.
    1. Coates AL, Leung K, Vecellio L, Schuh S. Testing of nebulizers for delivering magnesium sulfate to pediatric asthma patients in the emergency department. Respir Care. 2011;56(3):314–318. doi: 10.4187/respcare.00826.
    1. Dhand R. How should aerosols be delivered during invasive mechanical ventilation? Respir Care. 2017;62(10):1343–1367. doi: 10.4187/respcare.05803.
    1. Turker S, Dogru M, Yildiz F, Yilmaz SB. The effect of nebulised magnesium sulphate in the management of childhood moderate asthma exacerbations as adjuvant treatment. Allergol Immunopathol (Madr) 2017;45(2):115–120. doi: 10.1016/j.aller.2016.10.003.
    1. Bessmertny O, DiGregorio RV, Cohen H, et al. A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults. Ann Emerg Med. 2002;39(6):585–591. doi: 10.1067/mem.2002.123300.
    1. Aggarwal P, Sharad S, Handa R, Dwiwedi SN, Irshad M. Comparison of nebulised magnesium sulphate and salbutamol combined with salbutamol alone in the treatment of acute bronchial asthma: a randomised study. Emerg Med J. 2006;23(5):358–362. doi: 10.1136/emj.2005.026203.
    1. Knightly R, Milan SJ, Hughes R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2017;11(11):CD003898.
    1. Modaresi MR, Faghihinia J, Kelishadi R, Reisi M, Mirlohi S, Pajhang F, Sadeghian M. Nebulized magnesium sulfate in acute bronchiolitis: a randomized controlled trial. Indian J Pediatr. 2015;82(9):794–798. doi: 10.1007/s12098-015-1729-z.
    1. Dugernier J, Ehrmann S, Sottiaux T, Roeseler J, Wittebole X, Dugernier T, Jamar F, Laterre PF, Reychler G. Aerosol delivery during invasive mechanical ventilation: a systematic review. Crit Care. 2017;21(1):264. doi: 10.1186/s13054-017-1844-5.
    1. Cosa N, Costa E., Jr Inhaled pulmonary vasodilators for persistent pulmonary hypertension of the newborn: safety issues relating to drug administration and delivery devices. Med Devices (Auckl). 2016;9:45–51.
    1. Davis MD, Donn SM, Ward RM. Administration of inhaled pulmonary vasodilators to the mechanically ventilated neonatal patient. Pediatr Drugs. 2017;19(3):183–192. doi: 10.1007/s40272-017-0221-9.
    1. Berlinski A, Willis JR. Effect of tidal volume and nebulizer type and position on albuterol delivery in a pediatric model of mechanical ventilation. Respir Care. 2015;60(10):1424–1430. doi: 10.4187/respcare.04013.

Source: PubMed

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