Milrinone Versus Sildenafil in Treatment of Neonatal Persistent Pulmonary Hypertension: A Randomized Control Trial.

ABSTRACT: Persistent pulmonary hypertension of the newborn (PPHN) is a condition caused by failure of pulmonary vascular adaptation at birth, resulting in severe hypoxia. Several therapeutic modalities are being tried in developing countries where established therapies (inhaled nitric oxide and extracorporeal membrane oxygenation) are widely unavailable. This study aimed to assess the efficacy of milrinone versus sildenafil as available alternative therapeutics in treating PPHN. Forty neonates (>34 weeks) admitted to neonatal intensive care units with evidence of PPHN were randomly allocated to receive either oral sildenafil (0.5-2 mg/kg/6 hours) or intravenous milrinone (0.25-0.75 mic/kg/min). Primary outcomes included improvements in systolic pulmonary artery pressure and oxygen saturation index (OSI) at 24 and 48 hours after treatment. Secondary outcomes included the duration of hospitalization and mechanical ventilation. The ClinicalTrials identifier is NCT04391478. Both groups showed significant improvement in the post-treatment hemodynamic variables compared with pretreatment levels ( P < 0.05 for all parameters). Systolic pulmonary artery pressure and OSI values significantly improved in both study groups compared with baseline ( P < 0.001). The 24-hour and 48-hour post-treatment OSI values were much lower in the milrinone group than those in the sildenafil group ( P < 0.05). The length of hospital stay was significantly shorter in the milrinone group than that in the sildenafil group ( P < 0.05). There were no significant differences in the duration of mechanical ventilation, incidence of intracranial hemorrhage and pulmonary hemorrhage, or mortality between the 2 groups ( P > 0.05). In conclusion, milrinone and sildenafil are effective and well-tolerated in neonates with PPHN, particularly when inhaled nitric oxide and extracorporeal membrane oxygenation are not available. Milrinone is superior to sildenafil in improving oxygenation without lowering blood pressure parameters.

Enteral administration of a simulated amniotic fluid in preventing feeding intolerance in very low birthweight neonates: A randomized controlled trial.

OBJECTIVES: Feeding intolerance (FI) is a common finding in preterm neonates. Enteral administration of different forms of amniotic fluid (AF) has been tried for treating FI in high-risk neonates. Simulated amniotic fluid (SAF) is a solution with a similar electrolyte composition to human AF. The aim of this study was to examine whether enteral administration of SAF would improve feeding tolerance in very low birthweight (VLBW) neonates. METHODS: Forty VLBW neonates were randomized to either SAF or placebo (total daily dose 20 mL/kg/d-1 divided every 3 h) to their milk for a maximum of 7 d. Neonates with major congenital anomalies, those in whom early feeding was contraindicated, and those treated with parental erythropoietin and/or human granulocyte stimulating factor were excluded. The primary outcome was the total amount of enteral feeds reached by day 7. Secondary outcomes were incidence of FI and necrotizing enterocolitis (NEC). Study intervention was stopped on completing 7 d, reaching enteral feeds of 100 mL/kg/d-1, or the appearance of any sign of FI or NEC. RESULTS: All neonates tolerated the test solution well. The SAF group reached significantly larger volume and higher calories on days 3 and 7 (P < 0.05 for all). No statistical differences were seen between the two groups in incidence of FI (P = 0.311), NEC (P = 0.429), mortality (P = 0.632), length of stay (P = 0.744), or weight gain on day 10 (P = 0.389). Baseline hematologic parameters showed no statistical differences before or after enteral administration (P > 0.05). CONCLUSION: Results of the present study demonstrated that SAF solution might improve feeding tolerance in VLBW babies without evidence of its systemic absorption. Larger multicenter randomized studies are recommended.