Endotracheal Surfactant Combined With Budesonide for Neonatal ARDS

Abstract

Acute respiratory distress syndrome (ARDS) is a clinical condition characterized by acute diffuse inflammatory lung injury and severe hypoxemia. In 2017, the Montreux Consensus defined diagnostic criteria for ARDS in the neonatal period. The management of ARDS includes strict adherence to lung-protective ventilation strategies and therapeutic agents to improve gas exchange. We report two similar cases of premature infants with gestational ages of 23 and 24 weeks diagnosed with neonatal ARDS according to the Montreux definition. These patients developed acute worsening of oxygenation on the 30th and 28th day of life, respectively, while they were ventilated on volumeguarantee assist/control mode. Chest X-rays revealed bilateral diffuse opacity, there were no cardiogenic origins for pulmonary edema, and their oxygenation indexes were >8. Both cases fulfilled the neonatal ARDS criteria and the patients' clinical conditions were associated with late onset neonatal sepsis. After lung recruitment maneuver, the infants began HFO volume-guarantee ventilation and received surfactant treatment. Since they showed a poor short-term response, intratracheal surfactant of 100 mg/kg plus budesonide of 0.25 mg/kg were administered and their oxygenation indexes were reduced stepwise. Both patients survived and were discharged home with spontaneous breathing of room air. Neonatal ARDS is generally an underdiagnosed condition associated with sepsis, pneumonia, and meconium aspiration. Impaired surfactant activity and reduced lung compliance play important roles in its pathophysiology. To our knowledge, this is the first case report indicating the possible therapeutic role of budesonide plus surfactant in ARDS treatment. Since ARDS is an entity not recognized in newborns, we want to emphasize neonatal ARDS diagnosis and underline that the combination of budesonide and surfactant may be a novel therapeutic option in the treatment of ARDS.

Surfactant therapies for pediatric and neonatal ARDS: ESPNIC expert consensus opinion for future research steps

“…While these molecules have not yet reached clinical use, it is not surprising that budesonide, a well-known synthetic steroid, had been administered using surfactant as carrier. This gave promising results in neonates with NARDS [ 90 ]. Also, budesonide decreases the expression of secretory phospholipase A2 [ 91 ] and has a clinically significant anti-inflammatory effect in preterm neonates at risk of broncho-pulmonary dysplasia [ 92 ].…”

Antiviral Effect of Budesonide against SARS-CoV-2

“…COVID-19 has been associated with acute respiratory distress syndrome (ARDS), especially in severely ill patients [ 24 ]. Interestingly, some studies have investigated corticosteroids in the context of ARDS [ 25 , 26 ]. Mohamed and Meguid found that budesonide improved lung mechanics and oxygenation when patients with ARDS were nebulized with budesonide.…”

Efficacy of Intratracheal Budesonide-Surfactant Combined Therapy in Surfactant-Insufficient Rat Lungs with Lipopolysaccharide Insult

“…The use of surfactant as a vehicle to deliver steroids to the lungs of premature infants has been the subject of increasing clinical interest. 20 Several clinical studies have investigated the efficacy of this steroid delivery mode in preventing BPD 32 and chronic respiratory diseases 33 or in treating neonatal ARDS 34,35 in premature infants. Two recent meta-analysis studies reported that intratracheal instillation of steroid-surfactant combination was an effective therapy for preventing BPD in preterm infants with neonatal ARDS, but its benefit in reducing mortality was inconsistent.…”

“…[21][22][23][24] In animal studies, this steroid delivery mode has been used to investigate its efficacy in reducing ALI in animal models of surfactant-depleted lung diseases, 23,25 MAS, 26 hyperoxia 27 , and injurious mechanical ventilation. 28,29 In clinical studies, this steroid delivery mode has been used to prevent BPD [30][31][32] and chronic diseases 33 or to treat neonatal ARDS 34,35 in premature infants. However, no study has been conducted to investigate the therapeutic effect of this steroid delivery approach on LPS-induced ALI in surfactant-insufficiency lungs.…”