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
References
- Mathew B, Lakshminrusimha S. Persistent pulmonary hypertension in the newborn. Children. 2017;4(8):63. doi: 10.3390/children4080063.
- 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.
- Lakshminrusimha S, Keszler M. Persistent pulmonary hypertension of the newborn. Neorev. 2015;16(12):e680–e692. doi: 10.1542/neo.16-12-e680.
- 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.
- 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.
- 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.
- 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.
- 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.
- Kelly LE, Ohlsson A, Shah PS. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev. 2017;8(8):CD005494.
- 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.
- Ho JJ, Rasa G. Magnesium sulfate for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev. 2007;18(3):CD005588.
- 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.
- 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.
- 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.
- Hill NS, Preston IR, Roberts KE. Inhaled therapies for pulmonary hypertension. Respir Care. 2015;60(6):794–805. doi: 10.4187/respcare.03927.
- 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.
- Dhand R. How should aerosols be delivered during invasive mechanical ventilation? Respir Care. 2017;62(10):1343–1367. doi: 10.4187/respcare.05803.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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